Substituted pyridinone-pyridinyl compounds

ABSTRACT

The present disclosure provides pyridinone-pyridinyl compounds useful in the treatment of p38 kinase mediated diseases, such as lymphoma and auto-inflammatory disease, having the structure of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2 , R 3 , R 4 , R 5 , X and Y are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating p38 kinase mediated diseases using the compound.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/420,074, filed on Dec. 6, 2010. The entire disclosure of the aboveapplication is incorporated herein by reference.

FIELD

The present disclosure generally relates to a compound having enzymeinhibitory activity, pharmaceutical compositions comprising thecompound, and methods useful for treating diseases. More specifically,the present disclosure relates to a class ofpyrimidinone-phenyl-pyrimindinyl compounds, pharmaceutical compositionscomprising the compound, and methods useful for treating p38 kinasemediated diseases.

BACKGROUND

Mitogen-activated protein kinases (MAPK) are a conserved family ofenzymes that relay and propagate external stimuli, using phosphorylationcascades to generate a coordinated cellular response to the environment.The MAPK are proline-directed serine/threonine-specific protein kinasesthat regulate cellular activities, such as gene expression, mitosis,differentiation, and cell survival/apoptosis. To date, 4 distinctclasses of mammalian MAPK have been identified: the extracellularsignaling kinases (ERK1 and 2), the c-jun N-terminal kinase-1 (JNK1-3),the p38 MAPK (p38α, β, γ, and δ), and ERK5. The MAPK are activated bythe dual phosphorylation of Thr and Tyr residues within a TXY activationmotif by coordinated dual-specificity MAPKK, where X is Glu, Pro, andGly in ERK, JNK, and p38 MAPK, respectively. MAPK are 60-70% identicalto each other, yet differ in their activation loop sequences and sizes.The activation loop is adjacent to the enzyme-active site, and itsphosphorylation allows the enzyme to reposition active-site residuesinto the optimal orientation for substrate binding and catalysis.Downstream substrates of MAPK include mitogen-activatedprotein-kinase-activated protein (MAPKAP) kinases and transcriptionfactors, the phosphorylation of which, either directly or indirectly,regulates gene expression at several points, including transcription,nuclear export, and mRNA stability and translation. The cellularconsequences of MAPK activation include inflammation, apoptosis,differentiation, and proliferation.

Distinct genes encode 4 p38 MAPK in humans: p38α, β, γ, and δ.Significant amino acid sequence homology is observed among the 4isoforms, with 60%-75% overall sequence identity and >90% identitywithin the kinase domains. Tissue-selective expression is observed, withp38γ found predominantly in skeletal muscle, p38δ in the testes,pancreas, and small intestine. In contrast, p38α and β are moreubiquitously expressed.

An understanding of the broad biologic and pathophysiological roles ofp38 MAPK family members has grown significantly over the past decade, ashas the complexity of the signaling network leading to their activation.Scientific exploration of this pathway from biological, cellular, and invivo perspectives was largely enabled by the availability ofwell-behaved, selective, small-molecule inhibitors of p38 MAPK thattarget the α and, to a lesser extent, β isoforms. p38α MAPK is the majorisoform involved in the immune and inflammatory response. As such itsfunction is critical for the production and activity of multiplepro-inflammatory cytokines, including TNFα, IL-1, IL-6, and IL-8, incells such as macrophages, monocytes, synovial cells, and endothelialcells. p38 MAPK is also responsible for the induction of keyinflammatory enzymes such as COX2 and iNOS, the major sources ofeicosanoids and nitric oxide at sites of inflammation, respectively.Additionally, the p38 MAPK pathway regulates the expression of matrixmetalloproteinases (MMP), including MMP2, MMP9, and MMP13.

The use of selective and potent inhibitors has facilitated the discoveryof several families of p38 MAPK substrates, including transcriptionfactors, MAPKAP kinases, and other enzymes. p38 MAPK can directlyphosphorylate several transcription factors, such as myocyte-specificenhancer binding factor 2C (MEF2C), CHOP, peroxisomeproliferator-activated receptor (PPAR) α, PPAR γ co-activator 1 and p53.These transcription factors are involved in cellular functions such asapoptosis, gluconeogenesis, and synthesis of enzymes involved in fattyacid oxidation. p38 MAPK is also involved in the direct or indirectphosphorylation of enzyme substrates, such as cytosolic phospholipaseA2, and the Cdc25 phosphatases, which are involved in the activation ofcyclin-dependent protein kinase activity and cell-cycle regulation.Therefore in addition to its role in the inflammatory response, p38 MAPKhas other functions associated with normal and abnormal cell growth andsurvival as well as cellular function and homeostasis.

The MAPKAP kinases—MK2, MK-3, and PRAK—are selectively phosphorylated byp38 MAPK, while the phosphorylation of MSK1/2, MNK1/2, and RSKb iscatalyzed by both p38 MAPK and ERK. Activation of RSKb is thought toplay a role in cell survival, although the identification of substrateshas been difficult, due to the lack of specific inhibitors. MNK isinvolved in the phosphorylation of eukaryotic initiation factor-4E,which binds to the ‘cap’ structure of mRNA and enhances proteintranslation. MNK phosphorylates the mRNA binding protein hnRNP-A0, aprotein that regulates mRNA stability of transcripts encodinginflammatory proteins. MSK1/2 is involved in the phosphorylation of thetranscription factors CREB and ATF-1, which regulate AP-1 bindingproteins. In addition, MSK1/2 can phosphorylate Histone H3, which isinvolved in chromatin remodeling. While evidence suggests that MSK andMNK play a role in the mediation of pro-inflammatory cytokines, in vivodata with selective inhibitors and/or knockout mice are lacking.

MK-2, MK-3, and PRAK, once phosphorylated and activated by p38 MAPK,share similar substrate specificities. All of these kinases canphosphorylate the small heat-shock protein Hsp27. Studies have shownthat the PRAK- and MK3-deficient mice do not display any resistance toendotoxic shock or a decrease in lipopolysaccharide-(LPS)-inducedcytokine production. In contrast, MK-2-deficient mice show a resistanceto endotoxic shock and an impaired inflammatory response, as well as asignificantly decreased production of cytokines such as TNFα, IFNγ andIL-6. Thus, the p38/MK2 axis specifically is necessary and sufficientfor mediating pro-inflammatory responses.

Recently, Davidson et al (2004) Discovery and characterization of asubstrate selective p38alpha inhibitor, Biochemistry 43:11658-71,described a novel approach for increasing selectivity of a p38 MAPKinhibitors. In these studies, a high throughput screen was carried outusing an assay that measured the p38-dependent phosphorylation andactivation of MK2. The p38:MK2 complex is very stable with a Kd of 6 nM.The binding affinity of p38 for MK2 is driven by the C-terminal domainof MK2 containing several positively charged amino acid residues.Crystallographic studies of the p38:MK2 complex demonstrated that theC-terminal region of MK2 wraps around p38α and binds to the negativelycharged ED binding site. The tight binding of p38 to MK2 may give riseto conformational changes providing additional binding pockets forinhibitors that would specifically be dependent upon the p38:MK2interaction.

Taking advantage of the p38:MK2 interaction and using MK2 as the p38substrate, a novel inhibitor of p38α was discovered exhibitinginteresting properties (Davidson et al). This inhibitor demonstratedsubstrate selectivity by preventing the p38α dependent phosphorylationof MK2 (Ki app 300 nM) while sparing the p38α dependent phosphorylationof ATF2 (Ki app>20 uM). This novel inhibitor is functionally uniquecompared with traditional p38 ATP competitive inhibitors that block thep38-dependent phosphorylation of all p38 substrates. A secondindependent study also describes p38 inhibitors with unique mechanisticproperties. This work demonstrates a novel mechanism for the selectiveinhibition of the p38 dependent phosphorylation of MK2. Unlike theprevious study of Davidson et al., these mechanistically uniquecompounds are competitive with ATP and stabilize the p38/MK2 complex.Taken together, these two studies clearly prove the concept thatselective p38/MK2 axis blockade is achievable with small moleculeinhibitors. In comparison to traditional p38 MAPK inhibitors thesep38/MK2 inhibitors should retain or enhance potency and exhibit improvedsafety features in animal models of disease or in human clinicalsettings.

The p38/MK2 role in the regulation of inflammatory cytokines (TNFα,IL-1β, IL-6) and enzymes responsible for inflammation (COX-2, iNOS, andMMPs) makes it an attractive drug target. Several classical p38 MAPKinhibitors have progressed to testing in clinical trials. Some of thesecandidates have failed, for safety or other reasons, but several havereported clinical data in diseases such as rheumatoid arthritis, pain,Crohn's disease, acute coronary syndrome, multiple myeloma and chronicobstructive pulmonary disease. In addition to these diseases severalIL-1β mediated diseases could be impacted by a p38 inhibitor based uponthe key role for the p38 MAPK pathway in the biosynthesis and activityof this cytokine. These diseases include the family of cryopyrinassociated periodic disorders (CAPS), chronic gout, diabetes, Still'sdisease, Familial Mediterranean Fever among others.

In addition to human inflammatory pathways, p38 MAPK has been linked tocanine B cell growth and survival. The role of p38 MAPK in B cell growthsuggests that inhibition of this enzyme may be therapeuticallybeneficial for the treatment of canine B cell lymphoma. Canine lymphomais one of the most common malignancies diagnosed in companion animalsrepresenting 10-25% of canine neoplasms and >80% of the hematopoietictumors. An orally available, selective B cell growth inhibitor wouldmeet a significant unmet medical need.

Compounds useful for treating diseases and conditions caused orexacerbated by unregulated p38 MAP Kinase and/or TNF activity aredescribed in WO 2000/017175 published 30 Mar. 2000. The compoundsdescribed therein include a class of substituted urea compounds.

Compounds useful for treating diseases and conditions caused orexacerbated by unregulated p38 MAP Kinase and/or TNF activity aredescribed in WO 2000/071535 published 30 Nov. 2000. The compoundsdescribed therein include a class of indole-type compounds.

Compounds useful for treating diseases and conditions caused orexacerbated by unregulated p38 MAP Kinase and/or TNF activity aredescribed in WO 2002/042292 published 30 May 2002. The compoundsdescribed therein include a class of coupled indole-type derivatives.

Compounds useful for prophylaxis or treatment of circulatory diseases,metabolic diseases and/or central nervous system diseases are describedin WO 2008/062905 published 29 May 2008. The compounds described thereininclude an alkyl-pyrimidinone-phenyl compounds wherein the phenylfragment is substituted with a cyclopropyl radical, e.g.,6-butyl-3-(3-cyclopropylphenyl)-2-methyl-5-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadizol-3-yl)biphenyl-4-yl]methyl}pyrimidin-4(3H)-one.

Various potential inhibitors or modulators of p38 kinase and the p38kinase pathway are described in WO 2005/018557 published 3 Mar. 2005.The compounds described therein includedi-fluorophenyl-methoxy-pyridinone-pyridyl compounds wherein the pyridylfragment is substituted with various radicals including alkyl, alkenyl,hydroxyalkyl, halo, cyano, amino, carboxy, carbamoyl, methoxycarbonyland hydroxyalkenylimino radicals.

Compounds useful for treating diseases and conditions caused orexacerbated by unregulated p38 MAP Kinase and/or TNF activity aredescribed in US 2007/0167621 published 19 Jul. 2007. The compoundsdescribed therein include di-fluorophenyl-methoxy-pyrimidinone-phenylcompounds wherein the phenyl fragment is substituted with methyl amidoradical.

Compounds useful for treating diseases and conditions caused orexacerbated by unregulated p38 MAP Kinase and/or TNF activity aredescribed in WO 2004/087677 published 14 Oct. 2004. The compoundsdescribed therein include di-fluorophenyl-methoxy-pyrimidinone-phenylcompounds wherein the phenyl fragment is substituted with piperazinyl ora morpholinyl radical through a carbonyl bridge.

Pyrimidinone derivatives (as inhibitors of protein kinases and useful intreating disorders related to abnormal protein kinase activities such asinflammatory diseases and certain types of cancer), are described in WO2007/081901 published 19 Jul. 2008. The compounds described thereininclude di-fluorophenyl-methoxy-pyrimidinone-phenyl compounds whereinthe phenyl fragment is substituted with a cyclopropanyl or a morpholinylradical through an amidoalkylamido bridge.

Pyrimidinone derivatives (as inhibitors of protein kinases and useful intreating disorders related to abnormal protein kinase activities such asinflammatory diseases and certain types of cancer) are described in WO2008/153942 published 18 Dec. 2008. The compounds described thereininclude di-fluorophenyl-methoxy-pyrimidinone-phenyl compounds where thephenyl radical is substituted with cyclopentyl or a cyclohexyl radicalthrough an amido bridge.

Compounds useful for treating diseases and conditions caused orexacerbated by unregulated p38 MAP Kinase and/or TNF activity aredescribed in U.S. Pat. No. 7,067,540 published 27 Jun. 2007. Thecompounds described therein includedi-fluorophenyl-methoxy-pyridinone-phenyl compounds wherein the phenylradical is substituted with a five-membered heteroaryl radical (e.g.,pyrazolyl or imidazolyl).

SUMMARY

In one embodiment, there is provided a compound of Formula (I):

and a pharmaceutically acceptable salts thereof; wherein R¹, R², R³, R⁴,R⁵, X and Y are as defined in the detailed description.

In another embodiment, there is provided a pharmaceutical compositioncomprising a compound of Formula (I) or a pharmaceutically acceptablesalt thereof, and a pharmaceutically-acceptable carrier.

In various embodiments, the pharmaceutical composition further comprisesone or more additional pharmaceutically active compounds.

In yet another embodiment, there is provided a method for treating acondition comprising administering to a subject a therapeuticallyeffective amount of a compound of Formula (I), wherein the condition tobe treated includes, but is not limited to, autoimmune disorders,chronic inflammatory disorders, acute inflammatory disorders,auto-inflammatory disorders, pain, atherosclerosis, diabetes, fibroticdiseases, metabolic disorders, cancer, neoplasia, leukemia, andlymphoma.

In various embodiments, the method comprises administering a combinationof a compound of Formula (I) and at least one additionalpharmaceutically active compound.

In yet another embodiment, there is provided a method for preparing acompound of Formula (I) or a pharmaceutically acceptable salt thereof.

In yet another embodiment, there is provided an intermediate useful inmaking a compound of Formula (I) or a pharmaceutically acceptable saltthereof.

The compounds above are more fully described in the detailed descriptionthat follows.

DETAILED DESCRIPTION

The following description is merely exemplary in nature and is notintended to limit the present disclosure, application, or uses.

A. DEFINITIONS

The use of generic terms in the description of the compounds are hereindefined for clarity.

This specification uses the terms “substituent”, “radical”, “group”,“moiety”, and “fragment” interchangeably.

The term “hydrido” denotes a single —H atom (H) and may be usedinterchangeably with the symbol “H” or the term “hydrogen”.

If a substituent is described as being “optionally substituted,” thesubstituent may be either (1) not substituted or (2) substituted. If asubstitutable position is not substituted, the default substituent is ahydrido radical.

As used herein, the singular forms “a” and “an” may include pluralreference unless the context clearly dictates otherwise.

The term “alkyl”, either alone or within other terms such as “haloalkyl”and “alkylaryl”, refers to an acyclic alkyl radical containing 1, 2, 3,4, 5, 6, 7, 8, 9 or 10 carbon atoms. In some embodiments, alkyl is aC₁-C₁₀ alkyl group or a C₁-C₆ alkyl group. Examples of alkyl groupsinclude, but are not limited to, methyl, ethyl, propyl, isopropyl,butyl, isobutyl, t-butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl.

The term “alkoxy” is RO— where R is alkyl as defined herein.Non-limiting examples of alkoxy groups include methoxy, ethoxy andpropoxy. The terms alkyloxy and alkoxy may be used interchangeably.

The term “alkoxyalkyl” refers to an alkyl moiety substituted with analkoxy group. Examples of alkoxyalkyl groups include methoxymethyl,methoxyethyl, methoxypropyl and ethoxyethyl.

The term “aralkoxy” embraces an arylalkyl radical attached through anoxygen atom to the parent molecular scaffold. The terms “arylalkoxy” and“aralkoxy” may be used interchangeable.

The term “aryl” refers to any monocyclic, bicyclic or tricyclic carbonring of up to 6 atoms in each ring, wherein at least one ring isaromatic, or an aromatic ring system of 5 to 14 carbons atoms whichincludes a carbocyclic aromatic group fused with a 5- or 6-memberedcycloalkyl group. Examples of aryl groups include, but are not limitedto, phenyl, naphthyl, tetrahydronaphthyl and indanyl.

The term “arylalkyl” embraces an aryl-substituted alkyl radical and maybe used interchangeably with the term “aralkyl”. Examples includebenzyl, diphenylmethyl, triphenylmethyl, phenylethyl and diphenylethyl.The terms benzyl and phenylmethyl are interchangeable.

The term “aryloxy” is RO—, where R is aryl. “Arylthio” is RS—, where Ris aryl.

The term “aryloxyalkyl” embraces an aryloxy radical attached to an alkylgroup.

The term “cyano” denotes a carbon radical having 3 of 4 covalent bondsshared by a nitrogen atom.

The term “cycloalkyl” is a hydrocarbyl group containing at least onesaturated or partially unsaturated ring structure, and attached via aring carbon. In various embodiments, it refers to a saturated or apartially unsaturated C₃-C₁₂ cyclic moiety. Examples of cycloalkylgroups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl,cyclohexyl, cyclohexenyl, cycloheptyl and cyclooctyl.

The term “halo” refers to fluoro (—F), chloro (—Cl), bromo (—Br), oriodo (—I).

The term “haloalkyl” refers to an alkyl moiety substituted with one ormore halo groups. Examples of haloalkyl groups include —CF₃ and —CHF₂.

The term “haloaralkoxy” refers to aralkoxy group substituted with one ormore halo radicals. Examples of haloaralkoxy groups includefluorobenzyloxy, difluorobenzyloxy. In various embodiments of theinvention, haloaralkoxy is 4-fluorobenzyloxy or 2,4-difluorobenzyloxy.

The term “heterocyclyl” includes the heteroaryls defined below andrefers to a saturated or partially unsaturated monocyclic, bicyclic ortricyclic group of 2 to 14 ring-carbon atoms and, in addition toring-carbon atoms, 1 to 4 heteroatoms selected from P, N, O and S. Invarious embodiments the heterocyclic group is attached to another moietythrough carbon or through a heteroatom, and is optionally substituted oncarbon or a heteroatom. Examples of heterocyclyl include azetidinyl,benzoimidazolyl, benzofuranyl, benzofurazanyl, benzopyrazolyl,benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl,cinnolinyl, furanyl, imidazolyl, indolinyl, indolyl, indolazinyl,indazolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl,isoxazolyl, naphthpyridinyl, oxadiazolyl, oxazolyl, oxazoline,isoxazoline, oxetanyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl,pyridopyridinyl, pyridazinyl, pyridyl, pyrimidyl, pyrrolyl,quinazolinyl, quinolyl, quinoxalinyl, tetrahydropyranyl,tetrahydrothiopyranyl, tetrahydroisoquinolinyl, tetrazolyl,tetrazolopyridyl, thiadiazolyl, thiazolyl, thienyl, triazolyl,azetidinyl, 1,4-dioxanyl, hexahydroazepinyl, piperazinyl, piperidinyl,pyridin-2-onyl, pyrrolidinyl, morpholinyl, thiomorpholinyl,dihydrobenzoimidazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl,dihydrobenzoxazolyl, dihydrofuranyl, dihydroimidazolyl, dihydroindolyl,dihydroisooxazolyl, dihydroisothiazolyl, dihydrooxadiazolyl,dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl,dihydropyrimidinyl, dihydropyrrolyl, dihydroquinolinyl,dihydrotetrazolyl, dihydrothiadiazolyl, dihydrothiazolyl,dihydrothienyl, dihydrotriazolyl, dihydroazetidinyl,methylenedioxybenzoyl, tetrahydrofuranyl, and tetrahydrothienyl, andN-oxides thereof.

The term “heteroaryl” refers to a monocyclic, bicyclic or tricyclic ringhaving up to 6 atoms in each ring, wherein at least one ring is aromaticand contains from 1 to 4 heteroatoms in the ring selected from the groupconsisting of N, O and S, Non-limiting examples of heteroaryl includepyridyl, thienyl, furanyl, pyrimidyl, imidazolyl, pyranyl, pyrazolyl,thiazolyl, thiadiazolyl, isothiazolyl, oxazolyl, isoxazoyl, pyrrolyl,pyridazinyl, pyrazinyl, quinolinyl, isoquinolinyl, benzofuranyl,dibenzofuranyl, dibenzothiophenyl, benzothienyl, indolyl,benzothiazolyl, benzooxazolyl, benzimidazolyl, isoindolyl,benzotriazolyl, purinyl, thianaphthenyl and pyrazinyl. Attachment ofheteroaryl can occur via an aromatic ring, or, if heteroaryl is bicyclicor tricyclic and one of the rings is not aromatic or contains noheteroatoms, through a non-aromatic ring or a ring containing noheteroatoms. “Heteroaryl” is also understood to include the N-oxidederivative of any nitrogen containing heteroaryl.

The term “heteroaralkoxy” embraces a heteroarylalkyl radical attachedthrough an oxygen atom to the molecular scaffold. A class of preferredheteroaralkoxy radicals is “lower heteroaralkoxy” radicals having analkyl range of 1-3 carbon atoms. A preferred class ofC₆-heteroarylalkoxy radicals is (pyridin-2-yl)methoxy.

The term “heteroaryloxy” is RO—, where R is heteroaryl as definedherein. Examples include thiophen-2-yl-oxy, pyridin-2-yl-oxy,pyridin-3-yl-oxy, and pyridin-4-yl-oxy.

The term “heteroaryloxyalkyl” is a heteroaryloxy radical furtherattached to an alkyl radical.

The term “hydroxyl” refers to —OH radical and may be usedinterchangeably with “hydroxyl”.

The term “hydroxyalkyl” refers to a linear or branched monovalent C₁-C₁₀hydrocarbon group substituted with at least one hydroxy group andexamples of hydroxyalkyl groups include, but are not limited to,hydroxymethyl, hydroxyethyl, hydroxypropyl and hydroxybutyl.

The number of carbon atoms in a hydrocarbyl substituent can be indicatedby the prefix “C_(X)—C_(Y)” where X is the minimum and Y is the maximumnumber of carbon atoms in the substituent.

The term “pharmaceutically-acceptable” means suitable for use inpharmaceutical preparations, generally considered as safe for such use,officially approved by a regulatory agency of a national or stategovernment for such use, or being listed in the U.S. Pharmacopoeia orother generally recognized pharmacopoeia for use in animals, and moreparticularly in humans.

The term “pharmaceutically-acceptable salt” refers to a salt which mayenhance desired pharmacological activity. Examples ofpharmaceutically-acceptable salts include acid addition salts formedwith inorganic or organic acids, metal salts and amine salts. Examplesof acid addition salts formed with inorganic acids include salts withhydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid andphosphoric acid. Examples of acid addition salts formed with organicacids such as acetic acid, propionic acid, hexanoic acid, heptanoicacid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lacticacid, malonic acid, succinic acid, malic acid, maleic acid, fumaricacid, tartaric acid, citric acid, benzoic acid,o-(4-hydroxy-benzoyl)-benzoic acid, cinnamic acid, mandelic acid,methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid,2-hydroxyethane-sulfonic acid, benzenesulfonic acid,p-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid,p-toluenesulfonic acid, camphorsulfonic acid,4-methyl-bicyclo[2.2.2]oct-2-enel-carboxylic acid, gluco-heptonic acid,4,4′-methylenebis(3-hydroxy-2-naphthoic) acid, 3-phenylpropionic acid,trimethyl-acetic acid, tertiary butylacetic acid, lauryl sulfuric acid,gluconic acid, glutamic acid, hydroxy-naphthoic acids, salicylic acid,stearic acid and muconic acid. Examples of metal salts include saltswith sodium, potassium, calcium, magnesium, aluminum, iron, and zincions. Examples of amine salts include salts with ammonia and organicnitrogenous bases strong enough to form salts with carboxylic acids.

The term “therapeutically-effective amount” refers to an amount of acompound that, when administered to a subject for treating a disease, issufficient to effect treatment for the disease. “Therapeuticallyeffective amount” can vary depending on the compound, the disease andits severity, the age, the weight, etc. of the subject to be treated.

Compounds of the present invention can exist in tautomeric, geometric orstereoisomeric forms. The compounds' corresponding esters, metabolites,oximes, prodrugs, oniums and N-oxides are also embraced by theinvention. The present invention contemplates all such compounds,including cis- and trans-geometric isomers, E- and Z-geometric isomers,R- and S-enantiomers, diastereomers, d-isomers, 1-isomers, mixtures ofisomers and racemates thereof, as falling within the scope of theinvention.

The terms “cis” and “trans” denote a form of geometric isomerism inwhich two carbon atoms connected by a double bond will each have aradical atom on the same side of the double bond (“cis”) or on oppositesides of the double bond (“trans”).

Some of the compounds described contain one or more stereocenters andare meant to include R, S and mixtures of R and S forms for eachstereocenter present.

The compounds of the invention may also exist as atropisomers, i.e.,chiral rotational isomers. The invention encompasses the racemic,resolved atropisomers, and mixtures thereof.

B. COMPOUNDS

The present disclosure provides a compound having the structure ofFormula (I):

and a pharmaceutically acceptable salt thereof, wherein:

X and Y are independently selected from the group consisting of CH andN, with the proviso that when X is CH, Y is N, and when X is N, Y is CH;

R¹ is selected from the group consisting of —H, C₁-C₆-alkyl, and halo;

R² is selected from the group consisting of alkyl and alkoxy, whereinthe alkyl or alkoxy is optionally substituted with one or moresubstituents independently selected from the group consisting ofcycloalkyl, aryl, and heterocyclyl, and wherein the cycloalkyl or arylis optionally substituted with one or more substituents independentlyselected from the group consisting of alkyl, alkoxy and halo, andwherein the heterocyclyl is optionally substituted with one or moresubstituents independently selected from the group consisting of alkyl,alkoxy and cyano;

R³ and R⁴ are independently selected from the group consisting of —H,alkyl and halo; and

R⁵ is selected from the group consisting of cycloalkyl, aryl, andheterocyclyl, wherein the cycloalkyl or aryl is optionally substitutedwith one or more substituents independently selected from the groupconsisting of halo, cyano, alkyl, hydroxyalkyl, alkoxyalkyl andaminoalkyl, and wherein the heterocyclyl is optionally substituted withone or more substituents independently selected from the groupconsisting of cyano, alkyl, hydroxyalkyl, alkoxyalkyl and aminoalkyl.

In one embodiment of the compounds of Formula (I), X is CH and Y is N;R¹ is selected from the group consisting of C₁-C₃-alkyl, bromo, chloroand fluoro; R² is alkoxy, optionally substituted with one or moreheterocyclyl substituents optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁-C₃-alkyl and cyano; R³ is C₁-C₃-alkyl; R⁴ is selected from the groupconsisting of —H, C₁-C₃-alkyl, bromo, chloro and fluoro; and R⁵ isheterocyclyl optionally substituted with one or more substituentsindependently selected from the group consisting of alkyl, hydroxyalkyland aminoalkyl.

In another embodiment of the compounds of Formula (I), X is CH and Y isN; R¹ is methyl, bromo or chloro; R² is alkoxy optionally substitutedwith five- or six-membered heteroaryl optionally substituted with one ormore substituents independently selected from C₁-C₃-alkyl; R³ is methyl;R⁴ is —H, methyl or chloro; and R⁵ is five- or six-membered heteroaryloptionally substituted with one or more substituents independentlyselected from the group consisting of alkyl and hydroxyalkyl.

In still another embodiment of the compounds of Formula (I), X is CH andY is N; R¹ is methyl, bromo or chloro; R² is alkoxy substituted withfive-membered heteroaryl optionally substituted with one or more methylsubstituents; R³ is methyl; R⁴ is —H, methyl or chloro; and R⁵ ispyridine or pyrimidine, each of which is optionally substituted with oneor more substituents independently selected from the group consisting ofalkyl and hydroxyalkyl.

In another embodiment, there is provided a compound having the structureof Formula (II):

and a pharmaceutically acceptable salt thereof, wherein:

R¹ is methyl, bromo or chloro;

R⁴ is —H, methyl or chloro;

R²⁰ is five-membered heteroaryl optionally substituted with one or moremethyl groups;

R⁵⁰ is —H or methyl; and

R⁵¹ is —H, methyl or hydroxy.

Non-limiting examples of Formula (II) compounds include the followingcompounds and pharmaceutically acceptable salts thereof:

No. Compound Name 1.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 2.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 3.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 4.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 5.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 6.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 7.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 8.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 9.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 10.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 11.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 12.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 13.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 14.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; and 15.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one. 16.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 17.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 18.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 19.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 20.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 21.2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 22.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 23.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 24.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 25.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 26.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 27.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 28.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 29.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 30.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 31.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 32.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 33.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 34.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 35.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 36.2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 37.3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 38.3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 39.5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 40.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 41.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 42.2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 43.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 44.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 45.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 46.3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 47.3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 48.5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 49.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 50.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 51.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 52.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 53.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 54.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 55.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 56.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 57.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 58.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 59.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 60.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 61.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 62.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 63.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 64.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 65.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 66.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 67.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 68.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 69.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 70.2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 71.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 72.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 73.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 74.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 75.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 76.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 77.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 78.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 79.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 80.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 81.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 82.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 83.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 84.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H- [1,4′-bipyridin]-2-one; 85.2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 86.3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 87.3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 88.5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 89.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 90.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 91.2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 92.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 93.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 94.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 95.3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 96.3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 97.5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 98.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 99.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 100.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 101.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3- yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 102.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 103.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 104.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 105.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 106.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 107.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 108.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 109.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 110.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 111.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 112.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 113.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3- yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 114.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 115.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 116.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 117.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 118.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 119.2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 120.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 121.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 122.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 123.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 124.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 125.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 126.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 127.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 128.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 129.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 130.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 131.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 132.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 133.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 134.2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 135.3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 136.3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 137.5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 138.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 139.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 140.2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 141.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 142.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 143.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 144.3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 145.3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 146.5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 147.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 148.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 149.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 150.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 151.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 152.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 153.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 154.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 155.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 156.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 157.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 158.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 159.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 160.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 161.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 162.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 163.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 164.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 165.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 166.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 167.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 168.2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 169.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 170.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 171.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 172.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 173.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 174.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 175.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 176.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 177.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 178.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 179.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 180.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 181.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 182.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 183.2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 184.3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 185.3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 186.5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 187.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 188.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 189.2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 190.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 191.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 192.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 193.3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 194.3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 195.5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 196.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 197.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 198.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 199.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 200.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 201.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 202.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 203.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 204.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 205.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 206.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 207.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 208.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 209.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 210.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 211.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 212.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 213.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 214.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 215.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; and 216.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one.

In another embodiment of the compounds of Formula (I), X is N and Y isCH; R¹ is selected from the group consisting of C₁-C₃-alkyl, bromo,chloro and fluoro; R² is alkoxy, optionally substituted with one or moreheterocyclyl substituents optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁-C₃-alkyl and cyano; R³ and R⁴ are independently selected from thegroup consisting of —H and C₁-C₃-alkyl; and R⁵ is heterocyclyloptionally substituted with one or more substituents independentlyselected from the group consisting of alkyl, hydroxyalkyl andaminoalkyl.

In another embodiment of the compounds of Formula (I), X is N and Y isCH; R¹ is methyl or chloro; R² is alkoxy, optionally substituted withfive- or six-membered heteroaryl optionally substituted with one or moreC₁-C₃-alkyl groups; R³ is methyl; R⁴ is —H or methyl; and R⁵ is five- orsix-membered heteroaryl optionally substituted with one or moresubstituents independently selected from the group consisting of alkyland hydroxyalkyl.

In still another embodiment of the compounds of Formula (I), X is N andY is CH; R¹ is methyl or chloro; R² is alkoxy substituted withfive-membered heteroaryl optionally substituted with one or more methylsubstituents; R³ is methyl; R⁴ is —H or methyl; and R⁵ is pyridine orpyrimidine, wherein the pyridine or pyrimidine is optionally substitutedwith one or more substituents independently selected from the groupconsisting of alkyl and hydroxyalkyl.

The present invention is also directed to a subclass of compounds,including pharmaceutically acceptable salts of the compounds, whereinthe compounds have the structure of Formula (III):

wherein:

R¹ is methyl or chloro;

R⁴ is —H or methyl;

R²⁰ is five-membered heteroaryl optionally substituted with one or moremethyl groups; and

R⁵¹ is methyl or hydroxy.

Non-limiting examples of Formula (III) compounds include the followingcompounds and pharmaceutically acceptable salts thereof:

No. Compound Name 217.5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,3,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; 218.5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,3,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; 219.5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,3,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; 220.3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; 221.3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; 222.3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; 223.3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; 224.3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; 225.3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; 226.5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-2′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; 227.5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-2′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; 228.5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-2′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; 229.5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; 230.5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; and 231.5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one.

In another embodiment of the compounds of Formula (I), X is CH and Y isN; R¹ is selected from the group consisting of C₁-C₃-alkyl, bromo,chloro and fluoro; R² is alkoxy optionally substituted with one or moresubstituents selected from the group consisting of cycloalkyl and aryl;wherein the cycloalkyl or aryl is optionally substituted with one ormore substituents independently selected from the group consisting ofC₁-C₃-alkyl and halo; R³ and R⁴ are independently C₁-C₃-alkyl and —H;and R⁵ is selected from the group consisting of heterocyclyl optionallysubstituted with one or more substituents independently selected fromthe group consisting of alkyl, hydroxyalkyl and aminoalkyl.

In another embodiment of the compounds of Formula (I), X is CH and Y isN; R¹ is methyl, bromo or chloro; R² is alkoxy optionally substitutedwith phenyl optionally substituted with one or more halo substituents;R³ is methyl; R⁴ is —H, chloro or methyl; and R⁵ is five- orsix-membered heteroaryl optionally substituted with one or moresubstituents independently selected from the group consisting of alkyland hydroxyalkyl.

In another embodiment of the compounds of Formula (I), X is CH and Y isN; R¹ is methyl, bromo or chloro; R² is alkoxy substituted with phenyloptionally substituted with one or more substituents independentlyselected from the group consisting of chloro and fluoro; R³ is methyl;R⁴ is —H, chloro or methyl; and R⁵ is pyridine or pyrimidine, whereinthe pyridine and pyrimidine substituents is optionally substituted withone or more substituents independently selected from the groupconsisting of alkyl and hydroxyalkyl.

The present invention is also directed to a subclass of compounds,including pharmaceutically acceptable salts of the compounds, whereinthe compounds have the structure of Formula (IV):

wherein:

R¹ is methyl, bromo or chloro;

R⁴ is —H, chloro or methyl;

R⁵⁰ is —H or methyl; and

R⁵¹ is —H, methyl or hydroxy.

Non-limiting examples of Formula (IV) compounds include the followingcompounds and pharmaceutically acceptable salts thereof:

No. Compound Name 232.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 233.2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;234.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 235.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 236.2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((2,4-difluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 237.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 238.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 239.2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;240.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 241.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 242.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 243.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 244.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 245.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((2,4-difluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 246.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 247.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 248.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 249.3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 250.3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 251.4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;252.3-bromo-5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 253.3,5′-dichloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 254.5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 255.3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 256.3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;257.4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;258.3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 259.3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 260.4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 261.3-bromo-5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 262.3,5′-dichloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 263.5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 264.3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 265.3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 266.4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 267.3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 268.3-bromo-5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 269.3,5′-dichloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 270.5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 271.3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 272.3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 273.4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 274.3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 275.3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 276.4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 277.3-bromo-5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 278.3,5′-dichloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 279.5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 280.3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 281.3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 282.4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 283.4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 284.3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 285.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 286.3-chloro-4-((2,4-difluorobenzyl)oxy)-2″-(2-hydroxypropan-2-yl)-5′,6-dimethyl-2H-[1,4′:2′,4″-terpyridin]-2-one; and 287.2″-(tert-butyl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′:2′,4″-terpyridin]-2-one.

In another embodiment of the compounds of Formula (I), X is N and Y isCH; R¹ is selected from the group consisting of C₁-C₃-alkyl, bromo,chloro and fluoro; R² is alkoxy, optionally substituted with one or moresubstituents selected from the group consisting of cycloalkyl and aryl,wherein the cycloalkyl or aryl is optionally substituted with one ormore substituents independently selected from the group consisting ofC₁-C₃-alkyl and halo; R³ and R⁴ are independently C₁-C₃-alkyl and —H;and R⁵ is heterocyclyl optionally substituted with one or moresubstituents independently selected from the group consisting of alkyl,hydroxyalkyl and aminoalkyl.

In another embodiment of the compounds of Formula (I), X is N and Y isCH; R¹ is methyl or chloro; R² is alkoxy optionally substituted withphenyl optionally substituted with one or more halo substituents; R³ ismethyl; R⁴ is —H or methyl; and R⁵ is five- or six-membered heteroaryloptionally substituted with one or more substituents independentlyselected from the group consisting of alkyl and hydroxyalkyl.

In still another embodiment of the compounds of Formula (I), X is N andY is CH; R¹ is methyl or chloro; R² is alkoxy substituted with phenyloptionally substituted with one or more substituents independentlyselected from the group consisting of chloro and fluoro; R³ is methyl;R⁴ is —H or methyl; and R⁵ is pyridine or pyrimidine which is optionallysubstituted with one or more substituents independently selected fromthe group consisting of alkyl and hydroxyalkyl.

The present invention is also directed to a subclass of compounds,including pharmaceutically acceptable salts of the compounds, whereinthe compounds have the structure of Formula (V):

wherein:

Z is CH or N;

R¹ is methyl or chloro;

R⁴ is —H or methyl; and

R⁵¹ is methyl or hydroxy.

Non-limiting examples of Formula (V) compounds include the followingcompounds and pharmaceutically acceptable salts thereof:

No. Compound Name 288.4-((2,4-difluorobenzyl)oxy)-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-2H-[1,3′- bipyridin]-2-one; 289.4-((2,4-difluorobenzyl)oxy)-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,3,6-trimethyl-2H-[1,3′- bipyridin]-2-one; 290.3-chloro-4-((2,4-difluorobenzyl)oxy)-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,3′- bipyridin]-2-one; 291.3-chloro-4-((2,4-difluorobenzyl)oxy)-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,6-dimethyl-2H- [1,3′-bipyridin]-2-one; 292.5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,3′-bipyridin]-2- one; 293.5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-2′,6-dimethyl-2H-[1,3′-bipyridin]- 2-one; 294.3-chloro-4-((2,4-difluorobenzyl)oxy)-2″-(2-hydroxypropan-2-yl)-6-methyl-2H-[1,3′:5′,4″-terpyridin]-2- one; 295.3-chloro-4-((2,4-difluorobenzyl)oxy)-2″-(2-hydroxypropan-2-yl)-2′,6-dimethyl-2H-[1,3′:5′,4″- terpyridin]-2-one; 296.2″-(tert-butyl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,3′:5′,4″-terpyridin]-2-one; and 297.2″-(tert-butyl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-2′,6-dimethyl-2H-[1,3′:5′,4″-terpyridin]-2-one.

In another embodiment of the compounds of Formula (I), X and Y areindependently selected from the group consisting of CH and N, with theproviso that when X is CH, Y is N, and when X is N, Y is CH; R¹ isselected from the group consisting of C₁-C₃-alkyl, bromo, chloro andfluoro; R² is alkoxy optionally substituted with one or moresubstituents selected from the group consisting of cycloalkyl and aryl,wherein the cycloalkyl or aryl is optionally substituted with one ormore substituents independently selected from the group consisting ofC₁-C₃-alkyl and halo; R³ and R⁴ are independently C₁-C₃-alkyl, halo and—H; and R⁵ is heterocyclyl optionally substituted with one or moresubstituents independently selected from the group consisting of alkyl,hydroxyalkyl and aminoalkyl.

In another embodiment of the compounds of Formula (I), X and Y areindependently selected from the group consisting of CH and N, with theproviso that when X is CH, Y is N, and when X is N, Y is CH; R¹ ismethyl, bromo or chloro; R² is alkoxy optionally substituted with phenyloptionally substituted with one or more halo substituents; R³ is methyl;R⁴ is —H, chloro or methyl; and R⁵ is five- or six-membered heteroaryloptionally substituted with one or more substituents independentlyselected from the group consisting of alkyl and hydroxyalkyl.

In another embodiment of the compounds of Formula (I), X and Y areindependently selected from the group consisting of CH and N, with theproviso that when X is CH, Y is N, and when X is N, Y is CH; R¹ ismethyl, bromo or chloro; R² is alkoxy substituted with phenyl optionallysubstituted with one or more substituents independently selected fromthe group consisting of chloro and fluoro; R³ is methyl; R⁴ is —H,chloro or methyl; and R⁵ is pyridine or pyrimidine, wherein the pyridineor pyrimidine is optionally substituted with one or more substituentsindependently selected from the group consisting of alkyl andhydroxyalkyl.

The present invention is also directed to a subclass of compounds,including pharmaceutically acceptable salts of the compounds, whereinthe compounds have the structure of Formula (VI):

wherein

X and Y are independently selected from the group consisting of CH andN, with the proviso that when X is CH, Y is N, and when X is N, Y is CH;

R¹ is methyl, bromo or chloro;

R⁴ is —H, chloro or methyl;

R⁵⁰ is —H or methyl; and

R⁵¹ is —H, methyl or hydroxy.

Non-limiting examples of Formula (VI) compounds include the followingcompounds and pharmaceutically acceptable salts thereof:

No. Compound Name 298.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 299.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((4-fluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 300.2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;301.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 302.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 303.2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((4-fluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 304.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;305.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;306.2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;307.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 308.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((4-fluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 309.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 310.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 311.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 312.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((4-fluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 313.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 314.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 315.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 316.3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 317.3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 318.4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;319.3-bromo-5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 320.3,5′-dichloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 321.5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 322.3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;323.3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;324.4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;325.3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 326.3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 327.4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 328.3-bromo-5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 329.3,5′-dichloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 330.5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 331.3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 332.3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 333.4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 334.3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 335.3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 336.4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 337.3-bromo-5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 338.3,5′-dichloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 339.5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 340.3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 341.3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 342.4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 343.3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 344.3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 345.4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 346.3-bromo-5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 347.3,5′-dichloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 348.5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 349.3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; 350.3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one; and 351.4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one.

In another embodiment of the compounds of Formula (I), X and Y areindependently selected from the group consisting of CH and N, with theproviso that when X is CH, Y is N, and when X is N, Y is CH; R¹ isselected from the group consisting of C₁-C₃-alkyl, bromo, chloro andfluoro; R² is alkoxy optionally substituted with one or moresubstituents selected from the group consisting of cycloalkyl and aryl;wherein the cycloalkyl or aryl is optionally substituted with one ormore substituents independently selected from the group consisting ofC₁-C₃-alkyl and C₁-C₃-alkoxy; R³ and R⁴ are independently —H,C₁-C₃-alkyl, and halo; and R⁵ is heterocyclyl optionally substitutedwith one or more substituents independently selected from the groupconsisting of alkyl, hydroxyalkyl and aminoalkyl.

In another embodiment of the compounds of Formula (I), X and Y areindependently selected from the group consisting of CH and N, with theproviso that when X is CH, Y is N, and when X is N, Y is CH; R¹ ismethyl, bromo or chloro; R² is alkoxy optionally substituted with phenyloptionally substituted with one or more substituents independentlyselected from the group consisting of C₁-C₃-alkyl and C₁-C₃-alkoxy; R³is methyl; R⁴ is —H, chloro or methyl; and R⁵ is five- or six-memberedheteroaryl optionally substituted with one or more substituentsindependently selected from the group consisting of alkyl andhydroxyalkyl.

In another embodiment of the compounds of Formula (I), X and Y areindependently selected from the group consisting of CH and N, with theproviso that when X is CH, Y is N, and when X is N, Y is CH; R¹ ismethyl, bromo or chloro; R² is alkoxy, substituted with phenyloptionally substituted with one or more substituents independentlyselected from the group consisting of C₁-C₃-alkyl and C₁-C₃-alkoxy; R³is methyl; R⁴ is —H, chloro or methyl; and R⁵ is pyridine or pyrimidine,wherein the pyridine or pyrimidine is optionally substituted with one ormore substituents independently selected from the group consisting ofalkyl and hydroxyalkyl.

The present invention is also directed to a subclass of compounds,including pharmaceutically acceptable salts of the compounds, whereinthe compounds have the structure of Formula (VII):

wherein:

X and Y are independently selected from the group consisting of CH andN, with the proviso that when X is CH, Y is N, and when X is N, Y is CH;

R¹ is methyl, bromo or chloro;

R⁴ is —H, chloro or methyl;

R²¹ is methyl or methoxy;

R⁵⁰ is —H or methyl; and

R⁵¹ is —H, methyl or hydroxy.

Non-limiting examples of Formula (VII) compounds include the followingcompounds and pharmaceutically acceptable salts thereof:

No. Compound Name 352.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 353.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 354.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;355.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 356.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 357.2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 358.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;359.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;360.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;361.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 362.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 363.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 364.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 365.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 366.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 367.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 368.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 369.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 370.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 371.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 372.2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;373.3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 374.3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 375.5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 376.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;377.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;378.2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;379.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 380.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 381.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 382.3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 383.3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 384.5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 385.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 386.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 387.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 388.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 389.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 390.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 391.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 392.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 393.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 394.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 395.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 396.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 397.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 398.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 399.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 400.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 401.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 402.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 403.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; 404.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one; and 405.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one. 406.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 407.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 408.2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;409.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 410.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 411.2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 412.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 413.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 414.2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;415.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 416.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 417.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 418.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 419.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 420.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 421.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 422.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 423.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 424.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 425.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 426.2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;427.3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 428.3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 429.5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 430.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 431.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 432.2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;433.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 434.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 435.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 436.3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 437.3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 438.5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 439.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 440.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 441.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 442.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 443.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 444.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 445.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 446.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 447.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 448.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 449.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 450.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 451.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 452.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 453.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 454.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 455.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 456.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 457.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 458.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; and 459.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one.

In another embodiment of the compounds of Formula (I), X and Y areindependently selected from the group consisting of CH and N, with theproviso that when X is CH, Y is N, and when X is N, Y is CH; R¹ isselected from the group consisting of C₁-C₃-alkyl, bromo, chloro andfluoro; R² is alkoxy, optionally substituted with one or moreheterocyclyl substituents optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁-C₃-alkyl, C₁-C₃-alkoxy and cyano; R³ is C₁-C₃-alkyl; R⁴ is selectedfrom the group consisting of —H, C₁-C₃-alkyl, bromo, chloro and fluoro;and R⁵ is heterocyclyl optionally substituted with one or moresubstituents independently selected from the group consisting of alkyl,hydroxyalkyl and aminoalkyl.

In another embodiment of the compounds of Formula (I), X and Y areindependently selected from the group consisting of CH and N, with theproviso that when X is CH, Y is N, and when X is N, Y is CH; R¹ ismethyl, bromo or chloro; R² is alkoxy optionally substituted with five-or six-membered heteroaryl optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁-C₃-alkyl and C₁-C₃-alkoxy; R³ is methyl; R⁴ is —H, methyl or chloro;and R⁵ is five- or six-membered heteroaryl optionally substituted withone or more substituents independently selected from the groupconsisting of alkyl and hydroxyalkyl.

In another embodiment of the compounds of Formula (I), X and Y areindependently selected from the group consisting of CH and N, with theproviso that when X is CH, Y is N, and when X is N, Y is CH; R¹ ismethyl, bromo or chloro; R² is alkoxy substituted with six-memberedheteroaryl optionally substituted with one or more methyl substituentsindependently selected from the group consisting of C₁-C₃-alkyl andC₁-C₃-alkoxy; R³ is methyl; R⁴ is —H, methyl or chloro; and R⁵ ispyridine or pyrimidine, wherein the pyridine or pyrimidine is optionallysubstituted with one or more substituents independently selected fromthe group consisting of alkyl and hydroxyalkyl.

The present invention is also directed to a subclass of compounds,including pharmaceutically acceptable salts of the compounds, whereinthe compounds have the structure of Formula (VIII):

wherein:

X and Y are independently selected from the group consisting of CH andN, with the proviso that when X is CH, Y is N, and when X is N, Y is CH;

R¹ is methyl, bromo or chloro;

R⁴ is —H, methyl or chloro;

R²¹ is methyl or methoxy;

R⁵⁰ is —H or methyl; and

R⁵¹ is —H, methyl or hydroxy.

Non-limiting examples of Formula (VIII) compounds include the followingcompounds and pharmaceutically acceptable salts thereof:

No. Compound Name 460.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 461.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 462.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 463.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 464.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 465.2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 466.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 467.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 468.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 469.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 470.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 471.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 472.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 473.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 474.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 475.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 476.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 477.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 478.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 479.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 480.2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 481.3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 482.3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 483.5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 484.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 485.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 486.2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 487.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 488.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 489.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 490.3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 491.3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 492.5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 493.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 494.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 495.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 496.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 497.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 498.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 499.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 500.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 501.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 502.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 503.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 504.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 505.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 506.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 507.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 508.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 509.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 510.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 511.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; 512.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; and 513.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one. 514.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 515.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 516.2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 517.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 518.2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 519.2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 520.3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 521.2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 522.2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 523.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 524.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 525.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 526.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 527.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 528.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 529.3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 530.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 531.2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 532.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 533.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 534.2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 535.3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 536.3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 537.5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 538.3-bromo-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 539.3-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 540.2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 541.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 542.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 543.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 544.3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 545.3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 546.5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 547.3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 548.3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 549.2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 550.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 551.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 552.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 553.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 554.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 555.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 556.3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 557.3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 558.2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 559.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 560.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 561.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one; 562.3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 563.3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 564.5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one; 565.3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; 566.3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one; and 567.2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one.

C. METHODS OF TREATMENT

The present disclosure further provides methods for treating a conditionin a subject having or susceptible to having such a condition, byadministering to the subject a therapeutically-effective amount of oneor more compounds as described above. In one embodiment, the treatmentis preventative treatment. In another embodiment, the treatment ispalliative treatment. In another embodiment, the treatment isrestorative treatment.

1. Conditions

The conditions that can be treated in accordance with the presentinvention include, but are not limited to, autoimmune disorders, chronicinflammatory disorders, acute inflammatory disorders, auto-inflammatorydisorders, pain, atherosclerosis, diabetes, fibrotic diseases, metabolicdisorders, cancer, neoplasia, leukemia, lymphoma and the like.

In some embodiments the methods described herein are used to treatpatients with disorders arising from dysregulated cytokine, enzymesand/or inflammatory mediator production, stability, secretion,posttranslational processing. Examples of cytokines that may bedysregulated include interleukins 1, 2, 6, 8, 10, 12, 17, 22 and 23along with tumor necrosis factor alpha and interferons alpha, beta andgamma. Examples of inflammatory mediators that may be dysregulatedinclude nitric oxide, prostaglandins and leukotrienes. Examples ofenzymes include cyclo-oxygenase, nitric oxide synthase andmatrixmetalloprotease.

In some embodiments the methods described herein are used to treatpatients with dysregulated p38 activity, activation, biosynthesis orpathway function.

In some embodiments, the methods described herein are used to treat apatient in need thereof suffering from an autoimmune disorder, chronicand/or acute inflammatory disorder and/or auto-inflammatory disorder.Examples of disorders include, but are not limited to colitis, multiplesclerosis, arthritis, rheumatoid arthritis, osteoarthritis, juvenilearthritis, psoriatic arthritis, cryopyrin associated periodic syndromes,Muckle-Wells Syndrome, Familial Cold Auto-inflammatory Syndrome,neonatal-onset multisystem inflammatory disease, TNF receptor associatedperiodic syndrome, acute pancreatitis, chronic pancreatitis,atherosclerosis, inflammatory bowel disease, Crohn's disease, ulcerativecolitis, Diabetes mellitus type 1, Diabetes mellitus type 2, diabeticretinopathy, Still's disease, multiple sclerosis, vasculitis,sarcoidosis, pulmonary inflammation, acute respiratory distresssyndrome, wet and dry age-related macular degeneration, autoimmunehemolytic syndromes, autoimmune hepatitis, autoimmune neuropathy,autoimmune ovarian failure, autoimmune orchitis, autoimmunethrombocytopenia, reactive arthritis, ankylosing spondylitis, siliconeimplant associated autoimmune disease, Sjogren's syndrome, FamilialMediterranean Fever, systemic lupus erythematosus, vasculitis syndromes(such as, for example, giant cell arteritis, Behcet's disease &Wegener's granulomatosis), Vitiligo, secondary hematologic manifestationof autoimmune diseases (such as, for example, anemias), drug-inducedautoimmunity, Hashimoto's thyroiditis, hypophysitis, idiopathicthrombocytic pupura, metal-induced autoimmunity, myasthenia gravis,pemphigus, autoimmune deafness (including, for example, Meniere'sdisease), Goodpasture's syndrome, Graves' disease, HW-related autoimmunesyndromes and Gullain-Barre disease; Examples of inflammatory conditionsinclude, but are not limited to sepsis, septic shock, endotoxic shock,exotoxin-induced toxic shock, gram negative sepsis, toxic shocksyndrome, glomerulonephritis, peritonitis, interstitial cystitis,psoriasis, atopic dermatitis, hyperoxia-induced inflammations, asthma,chronic obstructive pulmonary disease (COPD), vasculitis, graft vs. hostreaction (i.e., graft vs. host disease), allograft rejections (e.g.,acute allograft rejection, and chronic allograft rejection), earlytransplantation rejection (e.g., acute allograft rejection), reperfusioninjury, acute pain, chronic pain, neuropathic pain, Fibromyalgia,pancreatitis, chronic infections, meningitis, encephalitis, myocarditis,gingivitis, post surgical trauma, tissue injury, traumatic brain injury,hepatitis, enterocolitis, sinusitis, uveitis, ocular inflammation, opticneuritis, gastric ulcers, esophagitis, peritonitis, periodontitis,dermatomyositis, gastritis, myositis, polymyalgia, pneumonia andbronchitis. Fibrotic diseases; Metabolic disorders, including but notlimited Obesity, steroid-resistance, glucose intolerance, metabolicsyndrome. In some embodiments, the methods described herein can be usedto treat a patient in need thereof and suffering from neoplasia.Examples of these conditions include but not limited to angiogenesis,multiple myeloma, leukemia, B cell lymphoma, T cell lymphoma, mast celltumors, lymphoma, Hodgkin's disease, cancer of the bone, mouth/pharynx,oesophagus, larynx, stomach, intestine, colon, rectum, lung, liver,pancreas, nerve, brain, head and neck, throat, ovary, uterus, prostate,testis, bladder, kidney, breast non-small cell lung carcinoma, melanoma,skin cancer, teratoma, rhabdomyosarcoma, glioma, metastatic and bonedisorders. In some embodiments, the disease associated with dysregulatedp38 include Cardiovascular and Cerebrovascular diseases, including butnot limited to Atherosclerosis, restenosis of an atheroscleroticcoronary artery, Acute coronary syndrome, myocardial infarction,cardiac-allograft vasculopathy and stroke; central nervous systemdisorders with an inflammatory or apoptotic component, Alzheimer'sdisease, Parkinson's disease, Huntington's disease, amyotrophic lateralsclerosis, spinal cord injury, neuronal ischemia and peripheralneuropathy. The term patient refers to both humans and nonhuman animalswith the abovementioned conditions. Nonhuman animals could be companionanimals such as, but not limited to canine and feline species.

2. Subjects

Suitable subjects to be treated according to the present inventioninclude mammalian subjects. Mammals according to the present inventioninclude, but are not limited to, human, canine, feline, bovine, caprine,equine, ovine, porcine, rodents, lagomorphs, primates, and the like, andencompass mammals in utero. Subjects may be of either gender and at anystage of development.

3. Administration and Dosing

The compounds of the present invention are generally administered in atherapeutically effective amount.

The compounds of the present invention can be administered by anysuitable route in the form of a pharmaceutical composition adapted tosuch a route, and in a dose effective for the treatment intended. Aneffective dosage is typically in the range of about 0.001 to about 100mg per kg body weight per day, preferably about 0.01 to about 30mg/kg/day, in single or divided doses. Depending on age, species andcondition being treated, dosage levels below the lower limit of thisrange may be suitable. In other cases, still larger doses may be usedwithout harmful side effects. Larger doses may also be divided intoseveral smaller doses, for administration throughout the day.

D. PHARMACEUTICAL COMPOSITIONS

For the treatment of the conditions referred to above, the compounds ofdescribed herein can be administered as follows:

Oral Administration

The compounds of the present invention may be administered orally,including by swallowing, so that the compound enters thegastrointestinal tract, or absorbed into the blood stream directly fromthe mouth (e.g., buccal or sublingual administration).

Suitable compositions for oral administration include solid formulationssuch as tablets, lozenges and capsules, which can contain liquids, gels,or powders.

Compositions for oral administration may be formulated as immediate ormodified release, including delayed or sustained release, optionallywith enteric coating.

Liquid formulations can include solutions, syrups and suspensions, whichcan be used in soft or hard capsules. Such formulations may include apharmaceutically acceptable carrier, for example, water, ethanol,polyethylene glycol, cellulose, or an oil. The formulation may alsoinclude one or more emulsifying agents and/or suspending agents.

In a tablet dosage form the amount of drug present may be from about0.05% to about 95% by weight, more typically from about 2% to about 50%by weight of the dosage form. In addition, tablets may contain adisintegrant, comprising from about 0.5% to about 35% by weight, moretypically from about 2% to about 25% of the dosage form. Examples ofdisintegrants include methyl cellulose, sodium or calcium carboxymethylcellulose, croscarmellose sodium, polyvinylpyrrolidone, hydroxypropylcellulose, starch and the like.

Suitable lubricants, for use in a tablet, may be present in amounts fromabout 0.1% to about 5% by weight, and include calcium, zinc or magnesiumstearate, sodium stearyl fumarate and the like.

Suitable binders, for use in a tablet, include gelatin, polyethyleneglycol, sugars, gums, starch, hydroxypropyl cellulose and the like.Suitable diluents, for use in a tablet, include mannitol, xylitol,lactose, dextrose, sucrose, sorbitol and starch.

Suitable surface active agents and glidants, for use in a tablet, may bepresent in amounts from about 0.1% to about 3% by weight, and includepolysorbate 80, sodium dodecyl sulfate, talc and silicon dioxide.

Parenteral Administration

Compounds of the present invention may be administered directly into theblood stream, muscle, or internal organs. Suitable means for parenteraladministration include intravenous, intra-muscular, subcutaneousintraarterial, intraperitoneal, intrathecal, intracranial, and the like.Suitable devices for parenteral administration include injectors(including needle and needle-free injectors) and infusion methods.

Compositions for parenteral administration may be formulated asimmediate or modified release, including delayed or sustained release.

Most parenteral formulations are aqueous solutions containingexcipients, including salts, buffering agents and carbohydrates.

Parenteral formulations may also be prepared in a dehydrated form (e.g.,by lyophilization) or as sterile non-aqueous solutions. Theseformulations can be used with a suitable vehicle, such as sterile water.Solubility-enhancing agents may also be used in preparation ofparenteral solutions.

Topical Administration

Compounds of the present invention may be administered topically to theskin or transdermally. Formulations for this topical administration caninclude lotions, solutions, creams, gels, hydrogels, ointments, foams,implants, patches and the like. Pharmaceutically acceptable carriers fortopical administration formulations can include water, alcohol, mineraloil, glycerin, polyethylene glycol and the like. Topical administrationcan also be performed by electroporation, iontophoresis, phonophoresisand the like.

Compositions for topical administration may be formulated as immediateor modified release, including delayed or sustained release.

E. COMBINATIONS AND COMBINATION THERAPY

The compounds of the present invention can be used, alone or incombination with other pharmaceutically active compounds, to treatconditions such as those previously described above. The compound(s) ofthe present invention and other pharmaceutically active compound(s) canbe administered simultaneously (either in the same dosage form or inseparate dosage forms) or sequentially. Accordingly, in one embodiment,the present invention comprises methods for treating a condition byadministering to the subject a therapeutically-effective amount of oneor more compounds of the present invention and one or more additionalpharmaceutically active compounds.

In another embodiment, there is provided a pharmaceutical compositioncomprising one or more compounds of the present invention, one or moreadditional pharmaceutically active compounds, and a pharmaceuticallyacceptable carrier.

In another embodiment, the one or more additional pharmaceuticallyactive compounds is selected from the group consisting ofanti-inflammatory drugs, anti-atherosclerotic drugs, immunosuppressivedrugs, immunomodulatory drugs, cytostatic drugs, anti-proliferativeagents, angiogenesis inhibitors, kinase inhibitors, cytokine blockersand inhibitors of cell adhesion molecules.

p38 inhibitor compositions described herein are also optionally used incombination with other therapeutic reagents that are selected for theirtherapeutic value for the condition to be treated In general, thecompositions described herein and, in embodiments where combinationaltherapy is employed, other agents do not have to be administered in thesame pharmaceutical composition, and, because of different physical andchemical characteristics, are optionally administered by differentroutes. The initial administration is generally made according toestablished protocols, and then, based upon the observed effects, thedosage, modes of administration and times of administration subsequentlymodified. In certain instances, it is appropriate to administer a p38inhibitor composition as described herein in combination with anothertherapeutic agent. By way of example only, if one of the side effectsexperienced by a patient upon receiving a p38 inhibitor composition asdescribed herein is rash, then it is appropriate to administer ananti-histamine agent in combination with the initial therapeutic agent.Or, by way of example only, the therapeutic effectiveness of a p38inhibitor is enhanced by administration of another therapeutic agent(which also includes a therapeutic regimen) that also has therapeuticbenefit. In any case, regardless of the disease, disorder or conditionbeing treated, the overall benefit experienced by the patient is eithersimply additive of the two therapeutic agents or the patient experiencesa synergistic benefit.

Therapeutically effective dosages vary when the drugs are used intreatment combinations. Methods for experimentally determiningtherapeutically effective dosages of drugs and other agents for use incombination treatment regimens are documented methodologies. Combinationtreatment further includes periodic treatments that start and stop atvarious times to assist with the clinical management of the patient. Inany case, the multiple therapeutic agents (one of which is a p38inhibitor as described herein) are administered in any order, or evensimultaneously. If simultaneously, the multiple therapeutic agents areoptionally provided in a single, unified form, or in multiple forms (byway of example only, either as a single pill or as two separate pills).

In some embodiments, one of the therapeutic agents is given in multipledoses, or both are given as multiple doses. If not simultaneous, thetiming between the multiple doses optionally varies from more than zeroweeks to less than twelve weeks.

In addition, the combination methods, compositions and formulations arenot to be limited to the use of only two agents, the use of multipletherapeutic combinations are also envisioned. It is understood that thedosage regimen to treat, prevent, or ameliorate the condition(s) forwhich relief is sought, is optionally modified in accordance with avariety of factors. These factors include the disorder from which thesubject suffers, as well as the age, weight, sex, diet, and medicalcondition of the subject. Thus, the dosage regimen actually employedvaries widely, in some embodiments, and therefore deviates from thedosage regimens set forth herein.

The pharmaceutical agents which make up the combination therapydisclosed herein are optionally a combined dosage form or in separatedosage forms intended for substantially simultaneous administration. Thepharmaceutical agents that make up the combination therapy areoptionally also administered sequentially, with either agent beingadministered by a regimen calling for two-step administration. Thetwo-step administration regimen optionally calls for sequentialadministration of the active agents or spaced-apart administration ofthe separate active agents. The time period between the multipleadministration steps ranges from, a few minutes to several hours,depending upon the properties of each pharmaceutical agent, such aspotency, solubility, bioavailability, plasma half-life and kineticprofile of the pharmaceutical agent. Circadian variation of the targetmolecule concentration is optionally used to determine the optimal doseinterval.

In another embodiment, a p38 inhibitor is optionally used in combinationwith procedures that provide additional or synergistic benefit to thepatient. A p38 inhibitor and the additional therapy(ies) are optionallyadministered before, during or after the occurrence of a disease orcondition, and the timing of administering the composition containing ap38 inhibitor varies in some embodiments. Thus, for example, a p38inhibitor is used as a prophylactic and is administered continuously tosubjects with a propensity to develop conditions or diseases in order toprevent the occurrence of the disease or condition. A p38 inhibitor andcompositions are optionally administered to a subject during or as soonas possible after the onset of the symptoms. While embodiments of thepresent invention have been shown and described herein, it will beobvious to those skilled in the art that such embodiments are providedby way of example only. Numerous variations, changes, and substitutionswill now occur to those skilled in the art without departing from theinvention. It should be understood that in some embodiments of theinvention various alternatives to the embodiments described herein areemployed in practicing the invention.

A p38 inhibitor can be used in combination with drugs from the followingclasses: NSAIDs, immunosuppressive drugs, immunomodulatory drugs,cytostatic drugs, anti-proliferative agents, angiogenesis inhibitors,biological agents, steroids, vitamin D3 analogs, retinoids, other kinaseinhibitors, cytokine blockers, corticosteroids and inhibitors of celladhesion molecules. Where a subject is suffering from or at risk ofsuffering from atherosclerosis or a condition that is associated withatherosclerosis, a p38 inhibitor composition described herein isoptionally used together with one or more agents or methods for treatingatherosclerosis or a condition that is associated with atherosclerosisin any combination. Examples of therapeutic agents/treatments fortreating atherosclerosis or a condition that is associated withatherosclerosis include, but are not limited to any of the following:torcetrapib, aspirin, niacin, HMG CoA reductase inhibitors (e.g.,atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin andsimvastatin), colesevelam, cholestyramine, colestipol, gemfibrozil,probucol and clofibrate.

Where a subject is suffering from or at risk of suffering from aninflammatory condition, a p38 inhibitor composition described herein isoptionally used together with one or more agents or methods for treatingan inflammatory condition in any combination. Examples of therapeuticagents/treatments for treating an autoimmune and/or inflammatorycondition include, but are not limited to any of the following:corticosteroids, nonsteroidal antiinflammatory drugs (NSAID) (e.g.ibuprofen, naproxen, acetaminophen, aspirin, Fenoprofen (Nalfon),Flurbiprofen (Ansaid), Ketoprofen, Oxaprozin (Daypro), Diclofenac sodium(Voltaren), Diclofenac potassium (Cataflam), Etodolac (Lodine),Indomethacin (Indocin), Ketorolac (Toradol), Sulindac (Clinoril),Tolmetin (Tolectin), Meclofenamate (Meclomen), Mefenamic acid (Ponstel),Nabumetone (Relafen), Piroxicam (Feldene), cox-2 inhibitors (e.g.,celecoxib (Celebrex))), immunosuppressants (e.g., methotrexate(Rheumatrex), leflunomide (Arava), azathioprine (Imuran), cyclosporine(Neoral, Sandimmune), tacrolimus and cyclophosphamide (Cytoxan), CD20blockers (Rituximab), Tumor Necrosis Factor (TNF) blockers (e.g.,etanercept (Enbrel), infliximab (Remicade) and adalimumab (Humira)),Abatacept (CTLA4-Ig) and interleukin-1 receptor antagonists (e.g.Anakinra (Kineret), interleukin 6 inhibitors (e.g., Actemra),interleukin 17 inhibitors (e.g., AlN457), Janus kinase inhibitors (e.g.,Tasocitinib), syk inhibitors (e.g. R788), chloroquine and itsderivatives.

For use in cancer and neoplastic diseases a p38 inhibitor is optimallyused together with one or more of the following classes of drugs:wherein the anti-cancer agent is an EGFR kinase inhibitor, MEKinhibitor, VEGFR inhibitor, anti-VEGFR2 antibody, KDR antibody, AKTinhibitor, PDK-1 inhibitor, PI3K inhibitor, c-kit/Kdr tyrosine kinaseinhibitor, Bcr-Abl tyrosine kinase inhibitor, VEGFR2 inhibitor,PDGFR-beta inhibitor, KIT inhibitor, Flt3 tyrosine kinase inhibitor,PDGF receptor family inhibitor, Flt3 tyrosine kinase inhibitor, RETtyrosine kinase receptor family inhibitor, VEGF-3 receptor antagonist,Raf protein kinase family inhibitor, angiogenesis inhibitor, Erb2inhibitor, mTOR inhibitor, IGF-1R antibody, NFkB inhibitor, proteosomeinhibitor, chemotherapy agent, or glucose reduction agent.

F. KITS

The present invention further comprises kits that are suitable for usein performing the methods of treatment or prevention described above. Inone embodiment, the kit contains a first dosage form comprising one ormore of the compounds of the present invention and a container for thedosage, in quantities sufficient to carry out the methods of the presentinvention.

G. INTERMEDIATES

In another embodiment, the invention relates to the novel intermediatesuseful for preparing the compounds of the present invention.

H. GENERAL SYNTHETIC SCHEMES

The compounds of the present invention can be prepared using the methodsillustrated in the general synthetic schemes and experimental proceduresdetailed below. These general synthetic schemes and experimentalprocedures are presented for purposes of illustration and are notintended to be limiting. The starting materials used to prepare thecompounds of the present invention are commercially available or can beprepared using routine methods known in the art.

Representative procedures for the preparation of compounds of inventionare outlined below in Schemes 1-3. The substituted pyridine startingmaterials can be purchased or prepared using methods known in the art.The synthesis of pyridinone intermediate 1c, can be accomplished by thereaction of 4-hydroxypyrone 1a with the amino-heteroaryl ester 1b.Halogenation of 1c using N-bromo or N-chlorosuccinimide in isopropanolor dichloroethane in the presence of acetic acid or dichloroacetic acidcan furnish halogenated pyridinone 1d. Benzylation of 1d withp-methoxybenzyl chloride can provide the p-methoxybenzyl etherrepresented by 1f.

Conventional hydrolysis of the ethyl ester 1f to the corresponding acidfollowed by acid chloride formation and reaction withN-methoxy-N-methylamine can provide the amide intermediate 1g. Methylketone 1h formation, using methylmagnesium bromide followed bycondensation with dit-butoxy-N,N-dimethyl would furnish the eneamineproduct represented by 1i. Condensation of the eneamine 1i with theamidine reagent in the presence of a base can provide the pyrimidineproduct 1j. Removal of the p-methoxybenzyl group under standard reactionconditions followed by alkylation with the appropriateheterocyclicmethyl halide can furnish the desired final productsrepresented by the formula 1k.

Compound 1k where R¹ is bromo or iodo, can also be used to obtaincompounds with R¹ having methyl or ethyl groups usingbis-(triphenylphosphine)palladium(II) chloride and triethylamine andhexamethylditin or trimethylsilylacetylene.

An alternative procedure for preparing the compounds of invention isoutlined in Scheme 2. The key amino-pyridine starting material 2d can beobtained from the appropriately substituted nitropyridine precursor bymethylation, followed by carbonylation and reduction using stannouschloride. The pyridinone product 2e can be obtained by the reaction of2d with the appropriately substituted 4-hydroxy pyrone derivative insolvents such as trifluoroethanol or dichlorobenzene in the presence oflithium chloride.

Halogenations of 2d using reagents such as N-bromosuccinimide orN-chlorosuccinimide would generate the desired products represented by2f. Elaboration of 2f to the final products represented by 21 can beachieved as described previously in scheme 1. The bromo intermediaterepresented by 2h (R¹=Br) can be used to introduce methyl or ethylgroups using bis-(triphenylphosphine)palladium (II) chloride andtriethylamine (US 2005/0176775) in solvents such as DMF, DMA oracetonitrile.

Scheme 3 outlines a potential route to obtain compounds of inventionwhere X═CH and Y═N. The preparation of the key aminopyridine precursor3c is described in U.S. Pat. No. 7,345,054. Condensation of 3c with thereagent derived from Meldrum's acid (US 2007/003993) can give thepyridinone product 3d. After the protection of the hydroxyl group in 3dusing p-methoxybenzylchloride in the presence of potassium carbonate,the resulting intermediate 3g can be converted to the correspondinghalogenated products represented by 3h using N-bromo orN-chlorosuccinimide. Intermediate 3h can be converted to the finalproducts represented by 3l by similar synthetic steps as described inSchemes 1 and 2.

Other appropriately substituted compounds of invention represented by4i, with R⁵ as aryl or five/six-membered heterocyclic groups can beobtained as shown in Scheme 4, starting from 4-hydroxypyrone and ahydroxyl-protected (silyl, i.e., SEM or THP) aminopyridine 4a.Halogenation to give 4c can be achieved as described in earlier schemes,using N-chloro or N-bromosuccinimide. Benzyl ether formation followed bydeprotection can generate the hydroxyl intermediate 4f. Triflateformation employing standard conditions can give 4g which upon palladiumcatalyzed cross-coupling reactions (Palladium in Heterocyclic chemistryby Jie Jack Li and Gordon W. Gribble) with a variety of aryl orheteroarylboronic acids, can give products represented by 4h. The finalcompounds of invention represented by 4i can be obtained by the removalp-methoxybenzyl followed by alkylation with appropriate heterocyclicmethyl halides.

The racemic product may be separated using a chiral chromatographycolumn such as Chiralcel OJ™ or Chiralpak® AD™ in a mobile phase ofethanol or methanol.

EXAMPLES

The following examples are merely illustrative, and do not limit thisdisclosure in any way.

Examples 1-567

Compounds I-567, each corresponding to Examples 1-567, are prepared inaccordance with Schemes Ito IV above.

Examples 284 and 285

Preparation of Compound 284 (i.e.,3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one)and Compound 285 (i.e.,2′-[2-(tert-butyl)pyrimidin-4-yl]-3-chloro-4-((2,4-difluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one)is described in the examples.

Step 1: Preparation of2′-chloro-4-hydroxy-5′,6-dimethyl-2H-1,4′-bipyridin-2-one. Awell-powdered mixture of 4-amino-5-methyl-2-chloropyridine (0.5 g, 3.5mmol), 4-hydroxy-6-methyl-pyrone (0.665 g, 5.3 mmol), and lithiumchloride (0.025 g, 0.6 mmol) was heated at 160° C. for 20 min in asealed tube. The resulting melt was cooled and the product was isolatedby silica gel flash chromatography using 3% methanol in dichloromethane.Appropriate fractions were combined, concentrated under reduced pressureand the resulting solid was triturated with ethyl acetate, cooled andfiltered. The solid was washed with ethyl acetate and dried to give0.053 g of the title compound as a yellow powder. ES-MS: m/z=251 (M+H).

NMR ¹H (300 MHz), CDCl₃ δ: 10.80 (br 1H), 8.47 (s, 1H), 7.56 (s, 1H),5.97 (br, 1H), 5.57 (d, 1H, J=2.4 Hz), 1.96 (s, 3H), and 1.83 (s, 3H).

Step 2: Preparation of2′-chloro-4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2H-1,4′-bipyridin-2-one.To a mixture of2-choloro-4-hydroxy-5′,6-dimethyl-2H-1-1,4-bipyridine-2-one (0.5 g, 0.6mmol) and 2,4-difluorobenzyl bromide (0.14 g, 0.67 mmol) indimethylformamide (3.0 mL), was added potassium carbonate (0.09 g, 0.65mmol) and stirred at room temperature for 4 h. The reaction mixture wasdiluted with water and extracted with ethyl acetate (3×10 mL).

The combined organic extracts were washed with water, dried (magnesiumsulfate) and concentrated to dryness. The resulting material waspurified by silica-gel flash chromatography using 35% heptane in ethylacetate. Appropriate fractions were combined, and concentrated underreduced pressure to give 0.17 g of the title compound as an amorphoussubstance. ES-Ms, m/z=377 (M+H), 399 (M+Na).

NMR ¹H (300 MHz), CDCl₃ δ: 8.43 (s, 1H), 7.41 (m, 1H), 7.16 (s, 1H),6.95 (m, 2H), 5.96 (m, 2H), 5.04 (s, 2H), 2.11 (s, 3H), and 1.89 (s,3H).

Step 3: Preparation of methyl4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2-oxo-2H-1,4′-bipyridine-2′-carboxylate.To a solution of2′-chloro-4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2H-1,4′-bipyridin-2-one(0.2 g, 0.53 mmol) in methanol (10.0 mL) in an autoclave vessel purgedwith nitrogen, was added (BINAP)PdCl₂ (0.021 g), followed by theaddition of triethyl amine (0.079 g, 0.78 mmol). The vessel waspressurized with carbon monoxide up to 30 psi and heated at 100° C. for16 h. The reaction mixture was cooled to room temperature, filteredthrough a celite pad and concentrated the filtrate to dryness. Theresidue was triturated with ethyl acetate and filtered. The filtrate wasconcentrated and the residue was purified by silica-gel flashchromatography using 3% methanol in ethyl acetate. Appropriate fractionswere combined and concentrated under reduced pressure to give 0.15 g ofthe title compound. ES-MS, m/z=401 (M+H).

NMR ¹H (300 MHz), CDCl₃ δ: 8.77 (s, 1H), 7.94 (s, 1H), 7.43 (m, 1H),6.98 (m, 2H), 5.98 (2s, 2H), 5.05 (s, 2H), 4.02 (s, 3H), 2.23 (s, 3H),and 1.86 (s, 3H).

Step 4: Preparation of methyl3-chloro-4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2-oxo-2H-1,4′-bipyridine-2′-carboxylate.A mixture of methyl4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2-oxo-2H-1,4′-bipyridine-2′-carboxylate(0.15 g, 0.375 mmol), N-chlorosuccinimide (0.06 g, 0.43 mmol) in2-propanol (3.0 mL) containing dichloroacetic acid (0.05 mL) was heatedat 60° C. under nitrogen for 2 h. The reaction mixture was concentrated,and the residue was purified by silica-gel flash chromatography using 4%methanol in ethyl acetate. Appropriate fractions were combined andconcentrated under reduced pressure to give 0.15 g of the titlecompound. ES-MS, m/z=435 (M+H).

NMR ¹H (300 MHz), CDCl₃ δ: 8.82 (s, 1H), 7.94 (s, 1H), 7.61 (m, 1H),7.01 (m, 1H), 6.98 (m, 1H), 6.23 (s, 1H), 5.31 (s, 2H), 4.04 (s, 3H),2.23 (s, 3H), and 1.97 (s, 3H).

Step 5: Preparation of3-chloro-4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2-oxo-2H-1,4′-bipyridine-2′-carboxylicacid. A mixture of methyl3-chloro-4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2-oxo-2H-1,4′-bipyridine-2′-carboxylate(0.13 g, 0.3 mmol) and 1.5 N NaOH (0.25 mL, 0.375 mmol) in dioxane (0.25mL) was heated at 60° C. for 1 h and stirred at room temperature for anadditional hr. The reaction mixture was acidified with acetic acid, andextracted with ethyl acetate (2×15 mL). The combined organic extractwere washed with water and concentrated under reduced pressure to givethe title compound as a white powder (0.08 g) which was used withoutpurification in the next step. ES-MS, m/z=421 (M+H).

Step 6: Preparation of3-chloro-4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2-oxo-2H-1,4′-bipyridine-2′-N-methoxymethylamide. To a solution of3-chloro-4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2-oxo-2H-1,4′-bipyridine-2′-carboxylicacid (0.08 g, 0.19 mmol) in dimethylformamide (1.0 mL) was addedcabonyldiimidazole (0.05 g, 0.31 mmol) and stirred at room temperature.After 1.5 h, the mixture was cooled in an ice-bath, addedN,O-dimethylhydroxylamine hydrochloride (0.03 g, 0.31 mmol), followed bythe addition of triethyl amine (0.045 mL, 0.32 mmol). The resultingmixture was stirred at 5° C. for 30 min, and at room temperature for 2h. At this stage, an additional 0.015 g of, N,O-dimethylhydroxylaminehydrochloride and triethyl amine (0.02 mL) were added and stirredovernight at room temperature. The reaction was quenched by the additionof ice-water (10 mL) and extracted with ethyl acetate (2×10 mL). Thecombined organic extracts were washed with water, and concentrated underreduced pressure to give the title compound as a white amorphousmaterial (0.09 g) which was used without purification in the next step.ES-MS, m/z=464 (M+H).

Step 7: Preparation of2′-acetyl-3-chloro-4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2H-1,4′-bipyridin-2-one.To a solution of3-chloro-4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2-oxo-2H-1,4′-bipyridine-2′-N-methoxymethylamide (0.09 g, 0.194 mmol) in tetrahydrofuran (2.0 mL) was addedmethylmagnesium bromide (0.08 mL, 3M, 0.24 mmol) and stirred at 0° C.After 1 h, added an additional 0.04 mL of methylmagnesium bromide andstirring was continued for an additional hr. The reaction was thenquenched by the addition of cold saturated ammonium chloride (5 mL) andextracted with ethyl acetate (2×10 mL). The combined organic extractswas washed with water, dried with magnesium sulfate and concentrated.The resulting residue was purified by silica-gel flash chromatographyusing 5% heptane in ethyl acetate. Appropriate fractions were combinedand concentrated under reduced pressure to give 0.055 g of the titlecompound. ES-MS, m/z=419 (M+H) and 441 (M+Na).

NMR ¹H (300 MHz), CDCl₃ δ: 8.72 (s, 1H), 7.80 (s, 1H), 7.61 (m, 1H),7.01 (m, 1H), 6.95 (m, 1H), 6.20 (s, 1H), 5.29 (s, 2H), 2.74 (s, 3H),2.21 (s, 3H), and 1.94 (s, 3H).

Step 8: Preparation of3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one(Example 284). To a solution of2′-acetyl-3-chloro-4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2H-1,4′-bipyridin-2-one(0.045 g, 0.11 mmol) in DMF (0.5 mL) was added N,N dimethylformamidedi-tert-butyl acetal (0.04 g, 0.2 mmol) and heated at 60° C. for 2 h.The reaction mixture was concentrated in vacuo, the residue was treatedwith toluene (1 mL) and concentrated in vacuo. The resulting residue wasdried in vacuo for 2 h, dissolved in DMF (1 mL), and potassium carbonate(0.03 g, 0.22 mmol) and 2-hydroxy-2-methylpropiamidine hydrochloride(0.02 g, 0.14 mmol) were added. This mixture was heated at 80° C. for 12h under nitrogen and concentrated in vacuo. The residue was partitionedbetween water (5 mL) and ethyl acetate (15 mL). The organic phase waswashed with water, dried with magnesium sulfate, and concentrated. Theresulting residue was purified by silica-gel flash chromatography using3% methanol in ethyl acetate. Appropriate fractions were combined andconcentrated under reduced pressure to give 0.022 g of the titlecompound. ES-MS, m/z=513 (M+H) and 535 (M+Na).

NMR ¹H (300 MHz), CDCl₃ δ: 8.88 (d, 1H, J=5.1 Hz), 8.77 (s, 1H), 8.28(d, 1H, J=5.1 Hz), 8.27 (s, 1H), 7.59 (m, 1H), 7.1 (m, 1H), 6.90 (m,1H), 6.25 (s, 1H), 5.31 (s, 2H), 4.75 (s, 1H), 2.21 (s, 3H), 2.01 (s,3H), 1.65 (s, 3H), and 1.64 (s, 3H).

Preparation of2′-[2-(tert-butyl)pyrimidin-4-yl]-3-chloro-4-((2,4-difluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one(Example 285). To a solution of2′-acetyl-3-chloro-4-[(2,4-difluorobenzyl)oxy]-5′,6-dimethyl-2H-1,4′-bipyridin-2-one(from step 7) (0.024 g, 0.057 mmol) in dimethylformamide (0.5 mL) wasadded N,N dimethylformamide di-tert-butyl acetal (0.02 g, 0.1 mmol) andheated at 60° C. for 2 h. The reaction mixture was concentrated invacuo, the residue was dissolved in toluene (1 mL) and the solvent wasremoved in vacuo. The resulting residue was dried in vacuo for 2 h. Itwas dissolved in DMF (1 mL) and potassium carbonate (0.025 g, 0.18 mmol)and 2,2,2-trimethylacetamidine hydrochloride (0.02 g, 0.14 mmol) wereadded. This mixture was heated at 80 C for 12 h under nitrogen. DMF wasremoved in vacuo and the residue was partitioned between water (5 mL)and ethyl acetate (15 mL). The organic phase was washed with water,dried with magnesium sulfate, and concentrated. The resulting residuewas purified by silica-gel flash chromatography using 3% methanol inethyl acetate. Appropriate fractions were combined and concentratedunder reduced pressure to give 0.011 g of the title compound. ES-MS,m/z=511 (M+H).

Example 568 Biological Assays

P38 inhibitory potency and P38/MK2 substrate selectivity: The novel, MK2substrate-selective inhibitory mechanism of compounds is evaluated inenzyme assays comparing inhibitor potency in blocking p38/MK2 versusp38/PRAK induced phosphorylation of an HSP-27 derived peptide substrate.The ability of compounds to inhibit activated phospho-p38α is evaluatedusing a p38α/MK2 and a p38α/PRAK cascade assay format. The kinaseactivity of p38α is determined by its ability to phosphorylate GST-MK2or GST-PRAK. Activation of MK2 or PRAK by p38α is quantitated bymeasuring the phosphorylation of a fluorescently-labeled, MK2 specificpeptide substrate, Hsp27 peptide (FITC-KKKALSRQLSVAA). Thephosphorylation of the Hsp27 peptide is quantified using the CaliperLabChip 3000. Kinase reactions is carried out in a 384-well plate(Matrical, MP101-1-PP) in 20 mM HEPES pH 7.5, 10 mM MgCl₂, 0.0005%Tween-20, 0.01% BSA, 1 mM DTT, and 2% DMSO. The inhibitor concentrationis varied between 0.02-30,000 nM, while the Hsp27 peptide substrate andMgATP are held constant at 1 μM and 10 μM, respectively. Activated p38αis added to a final concentration of 20 μM for reactions withnonphosphorylated 1 nM His6-MK2 in the cascade reaction. For thep38α/PRAK cascade, unactivated GST-PRAK is held constant at 1 nM whilep38α is added in to a final concentration of 20 pM. Kinase reactions areincubated at room temperature and quenched after 30 minutes by theaddition of stop buffer (180 mM HEPES, 30 mM EDTA, and 0.2% CoatingReagent-3). Under these conditions, approximately 20% of the substrateHsp27 peptide is phosphorylated. Reactions are initiated by the additionof activated p38α except for preincubation experiments, where reactionsare initiated by the addition of Hsp27 peptide and MgATP. Preincubationof p38α with inhibitor or p38a with unactivated His6-MK2 or unactivatedGST-PRAK and inhibitor are performed at 2× final assay concentrations atroom temperature 240 minutes prior to adding ATP and Hsp27 peptide toinitiate catalysis. The p38α compound inhibitory potency is quantitatedfrom dose-response IC50 values or Ki values from p38α/MK2 cascade assayswhile the substrate selectivity is calculated as a ratio ofp38α/PRAK:p38α/MK2 IC50 values. Species compounds of Formula (I),described hereinabove, evaluated in this assay, are expected to providea therapeutic benefit in the treatment of p38 kinase mediated diseases,such as autoimmune diseases and lymphoma.

Compounds were tested in accordance with the above described assay,yielding the IC50 values described below:

p38/MK2 p38/PRAK Example Structure Name MW IC₅₀ (μM) IC₅₀ (μM) 284

3-chloro-4-((2,4- difluorobenzyl)oxy)-2′- (2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)- 5′-6-dimethyl-2H-[1,4′- bipyridin]-2-one 5120.0064/0.0073 0.138/0.144 285

2′-(2-(tert- butyl)pyrimidin-4-yl)- 3-chloro-4-((2,4-difluorobenzyl)oxy)- 5′,6-dimethyl-2H-[1,4′- bipyridin]-2-one 5100.018/0.026 0.121/0.210

Cytokine regulation in human monocytes: The p38 pathway has been shownto be critical for the biosynthesis of a number of proinflammatorycytokines including TNFα, IL-β and IL-6. Evaluation of the potency andefficacy of p38 inhibitors to block cytokine production is carried outusing the human U937 cell line. The U937 human pre-monocytic cell lineis obtained from the American Type Culture Collection (Rockville, Md.).These cells are differentiated to a monocytic/macrophage phenotype asdescribed by Burnette (Burnette et al, (2009). SD0006: a potent,selective and orally available inhibitor of p38 kinase, Pharmacology84(1):42-60). Differentiated U937 cells are seeded into 96-well tissueculture plates (200,000 cells/well) in complete media. After 24 hours,the cells are pretreated for 60 minutes in the presence or absence ofcompound and then stimulated with LPS (0.1 μg/mL) for 4 hours. Culturemedia are then collected for determination of TNFα, IL-6 or IL-1β levelsby ELISA. Cytokine concentrations are extrapolated from recombinantprotein standard curves using a four-parameter logistic model andsolving for IC₅₀ after iterating to the best least-squares fit. Speciescompounds of Formula (I), described hereinabove, evaluated in thisassay, are expected to provide a therapeutic benefit in the treatment ofp38 kinase mediated diseases, such as lymphoma or inflammation.

IL1β induced prostaglandin production in Rheumatoid arthritis synovialfibroblasts (RASF): Rheumatoid arthritis synovial fibroblasts (RASF) arederived from the inflamed synovium of a female RA patient who wasundergoing total knee replacement. Synovial tissue is teased away fromadjacent cartilage and dispersed into single cells with collagenase.Cells are expanded and banked. RASF cells are further cultured asdescribed by Burnette supra. RASF cells are seeded into 96-well tissueculture plates (5×10⁴ cells/well) in complete growth medium. After 24hours, the medium is replaced with fresh growth medium containing 1%FBS. Cells are treated with serial concentrations (30,000-0.01 nM) ofcompound or dimethyl-sulfoxide (DMSO) vehicle control for 1 hour thenstimulated with 1 ng/mL IL-1β (R&D Systems, Minneapolis, Minn.) for18-20 hours at 37° C. and conditioned media collected. PGE₂ levels thein cultured media are quantitated by ELISA (Cayman Chemical, Ann Arbor,Mich.). Species compounds of Formula (I), described hereinabove,evaluated in this assay, are expected to provide a therapeutic benefitin the treatment of p38 kinase mediated diseases, such as lymphoma orrheumatoid arthritis.

Substrate selectivity in HUVEC cells: When a compound is identified fromthe biochemical characterization step with selective inhibition ofp38/MK2, it is next placed into a cell-based assay to verify enzyme tocell translatability. These assays utilize human umbilical veinendothelial cells (HUVEC) to demonstrate inhibition of Hsp27phosphorylation (a biomarker of p38/MK2 activation) while sparingproduction of tissue factor (TF), which is linked to another downstreamsubstrate of p38, MSK. In a 96-well format, adherent HUVEC (at 5passages or less) are treated for 1 hour with serially-dilutedcompounds, including a non-selective p38 inhibitor as a reference, orvehicle for controls. For Hsp27 phosphorylation, cells are thenstimulated with 500 pg/mL IL-1β for 0.5 hours, media is removed, cellsare lysed, and phospho-Hsp27 in the lysate is quantitated byenzyme-linked immunosorbent assay (ELISA) (Life Technologies, Carlsbad,Calif.). The procedure for TF release is a similar ELISA-based assay(American Diagnostica, Stanford, Conn.), except that IL-1β stimulationproceeds for 5 hours. The ratio of TF inhibition IC50:HSP27phosphorylation inhibition IC50 is defined as the substrate selectivityindex in these cells. Species compounds of Formula (I), describedhereinabove, evaluated in this assay, are expected to provide atherapeutic benefit in the treatment of p38 kinase mediated diseases,such as lymphoma and autoinflammatory disease.

Canine B cell growth regulation: p38 inhibitors have been shown touniquely inhibit canine B cell proliferation and survival. Thisselective effect on canine B cells may be exploited in therapeutictreatment for canine B cell lymphoma, a fatal disease thatimpacts >40,000 companion animals in the United States. Quantitation ofimpact of p38 inhibitors on B cell growth is a cellular indicator ofefficacy in B cell lymphoma. Species compounds of Formula (I), describedhereinabove, evaluated in this assay, are expected to provide atherapeutic benefit in the treatment of p38 kinase mediated diseases,such as lymphoma. These assays utilize beagle dog spleens obtained withprotocols approved by the Saint Louis University Animal Care and UseCommittee in collaboration with Seventh Wave Laboratories. Leukocytesare isolated from splenocytes by centrifugation through Histopaque 1077.To evaluate effect on proliferation, leukocytes are then cultured for 48hours in 96-well plates in the presence of vehicle or test compounds.Cells are stimulated with LPS for TLR4 stimulation, Staphylococcusaureus B cell mitogen, or concanavalin-A T cell mitogen, thenproliferation is quantitated with a BRDU incorporation ELISA (Roche,Mannheim, Germany). For apoptosis experiments, leukocytes are plated on96-well polypropylene U bottom plates and treated with p38 MAPKinhibitors or staurosporine (as a positive control) for up to 24 hoursin the absence or presence of actinomycin D or cycloheximide (if neededto increase apoptosis rate). Apoptosis is determined using Caspase-Glo3/7 luminescent assay (Promega, Madison, Wis.). In both assays, valuesgenerated after incubation with increasing concentrations of theinhibitors are compared to a negative control without inhibitors.

LPS Induced TNFα Production in rats: Rats are fasted eighteen hoursprior to oral dosing, and allowed free access to water throughout theexperiment. Each treatment group consists of five animals. Compounds areprepared as a suspension in a vehicle consisting of 0.5%methylcellulose, (Sigma Aldrich, St. Louis, Mo.), 0.025% Tween 20 (SigmaAldrich). The compound or vehicle is administered by oral gavage in avolume of 1 mL. Two vehicle groups are used per experiment to controlfor intra-experiment variability. LPS (E. coli serotype 0111:B4, SigmaAldrich) is administered four hours after compound intravenous injectionat a dose of 1 mg/kg in 0.5 mL sterile saline (Baxter Healthcare,Deerfield, Ill.). Blood is collected in serum separator tubes viacardiac puncture ninety minutes after LPS injection, a time pointcorresponding to maximal TNFα and IL-1β production. After clotting,serum is withdrawn and stored at −20° C. and IL-1β and TNFα levelsquantitated by ELISA (Burnette supra). Species compounds of Formula (I),described hereinabove, evaluated in this assay, are expected to providea therapeutic benefit in the treatment of p38 kinase mediated diseases,such as lymphoma or inflammation.

All mentioned documents are incorporated by reference as if hereinwritten. When introducing elements of the present invention or theexemplary embodiment(s) thereof, the articles “a,” “an,” “the” and“said” are intended to mean that there are one or more of the elements.The terms “comprising,” “including” and “having” are intended to beinclusive and mean that there may be additional elements other than thelisted elements. Although this invention has been described with respectto specific embodiments, the details of these embodiments are not to beconstrued as limitations.

1. A compound having the structure of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein: X and Y areindependently selected from the group consisting of CH and N, with theproviso that when X is CH, Y is N, and when X is N, Y is CH; R¹ isselected from the group consisting of C₁-C₆-alkyl, halo and —H; R² isselected from the group consisting of alkyl and alkoxy; wherein thealkyl or alkoxy is optionally substituted with one or more substituentsindependently selected from the group consisting of cycloalkyl, aryl,and heterocyclyl; and wherein the cycloalkyl or aryl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of alkyl, alkoxy and halo; and wherein theheterocyclyl is optionally substituted with one or more substituentsindependently selected from the group consisting of alkyl, alkoxy andcyano; R³ and R⁴ are independently selected from the group consisting ofalkyl, halo and —H; and R⁵ is selected from the group consisting ofcycloalkyl, aryl, and heterocyclyl; wherein the cycloalkyl or aryl isoptionally substituted with one or more substituents independentlyselected from the group consisting of halo, cyano, alkyl, hydroxyalkyl,alkoxyalkyl and aminoalkyl; and wherein the heterocyclyl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of cyano, alkyl, hydroxyalkyl, alkoxyalkyl andaminoalkyl.
 2. The compound according to claim 1, wherein X is CH and Yis N.
 3. The compound according to claim 2, wherein: R¹ is selected fromthe group consisting of C₁-C₃-alkyl, bromo, chloro and fluoro; R² isalkoxy, optionally substituted with one or more heterocyclylsubstituents optionally substituted with one or more substituentsindependently selected from the group consisting of C₁-C₃-alkyl andcyano; R³ is C₁-C₃-alkyl; R⁴ is selected from the group consisting of—H, C₁-C₃-alkyl, bromo, chloro and fluoro; and R⁵ is heterocyclyloptionally substituted with one or more substituents independentlyselected from the group consisting of alkyl, hydroxyalkyl andaminoalkyl.
 4. The compound according to claim 3, wherein: R¹ is methyl,bromo or chloro; R² is alkoxy optionally substituted with five- orsix-membered heteroaryl optionally substituted with one or moresubstituents independently selected from C₁-C₃-alkyl; R³ is methyl; R⁴is —H, methyl or chloro; and R⁵ is five- or six-membered heteroaryloptionally substituted with one or more substituents independentlyselected from the group consisting of alkyl and hydroxyalkyl.
 5. Thecompound according to claim 4, wherein: R² is alkoxy substituted withfive-membered heteroaryl optionally substituted with one or more methylsubstituents; and R⁵ is pyridine or pyrimidine, wherein the pyridine orpyrimidine is optionally substituted with one or more substituentsindependently selected from the group consisting of alkyl andhydroxyalkyl.
 6. The compound according to claim 5, wherein the compoundhas the structure of Formula (II):

wherein: R¹ is methyl, bromo or chloro; R⁴ is —H, methyl or chloro; R²⁰is five-membered heteroaryl optionally substituted with one or moremethyl substituents; R⁵⁰ is —H or methyl; and R⁵¹ is —H, methyl orhydroxy.
 7. The compound according to claim 6, selected from the groupconsisting of:2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;and3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one.8. The compound according to claim 6, selected from the group consistingof:3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;and2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one.9. The compound according to claim 6, selected from the group consistingof:3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;and2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one.10. A compound according to claim 6, selected from the group consistingof:3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;and2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one.11. The compound according to claim 6, selected from the groupconsisting of:3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;and2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one.12. The compound according to claim 1, wherein X is N and Y is CH. 13.The compound according to claim 12, wherein: R¹ is selected from thegroup consisting of C₁-C₃-alkyl, bromo, chloro and fluoro; R² is alkoxy,optionally substituted with one or more heterocyclyl optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁-C₃-alkyl and cyano; R³ and R⁴ areindependently selected from the group consisting of —H and C₁-C₃-alkyl;and R⁵ is heterocyclyl optionally substituted with one or moresubstituents independently selected from the group consisting of alkyl,hydroxyalkyl and aminoalkyl.
 14. The compound according to claim 13,wherein: R¹ is methyl or chloro; R² is alkoxy optionally substitutedwith five- or six-membered heteroaryl optionally substituted with one ormore substituents independently selected from C₁-C₃-alkyl; R³ is methyl;R⁴ is —H or methyl; and R⁵ is five- or six-membered heteroaryloptionally substituted with one or more substituents independentlyselected from the group consisting of alkyl and hydroxyalkyl.
 15. Thecompound according to claim 14, wherein: R² is alkoxy substituted withfive-membered heteroaryl optionally substituted with one or more methylsubstituents; and R⁵ is pyridine or pyrimidine, wherein the pyridine orpyrimidine is optionally substituted with one or more substituentsindependently selected from the group consisting of alkyl andhydroxyalkyl.
 16. The compound according to claim 15, wherein thecompound has the structure of Formula (III):

wherein: R¹ is methyl or chloro; R⁴ is —H or methyl; R²⁰ isfive-membered heteroaryl optionally substituted with one or more methylsubstituents; and R⁵¹ is methyl or hydroxy.
 17. The compound accordingto claim 16, selected from the group consisting of:5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,3,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,3,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,3,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-2′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-2′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-2′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;and5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one.18. The compound according to claim 2, wherein: R¹ is selected from thegroup consisting of C₁-C₃-alkyl, bromo, chloro and fluoro; R² is alkoxy,optionally substituted with one or more substituents selected from thegroup consisting of cycloalkyl and aryl; wherein the cycloalkyl or arylis optionally substituted with one or more substituents independentlyselected from the group consisting of C₁-C₃-alkyl and halo; R³ and R⁴are independently C₁-C₃-alkyl, halo and —H; and R⁵ is heterocyclyloptionally substituted with one or more substituents independentlyselected from the group consisting of alkyl, hydroxyalkyl andaminoalkyl.
 19. The compound according to claim 18, wherein: R¹ ismethyl, bromo or chloro; R² is alkoxy optionally substituted with five-or six-membered aryl optionally substituted with one or more halosubstituents; R³ is methyl; R⁴ is —H, chloro or methyl; and R⁵ is five-or six-membered heteroaryl optionally substituted with one or moresubstituents independently selected from the group consisting of alkyland hydroxyalkyl.
 20. The compound according to claim 19, wherein: R² isalkoxy substituted with phenyl optionally substituted with one or moresubstituents independently selected from the group consisting of chloroand fluoro; and R⁵ is pyridine or pyrimidine, wherein the pyridine orpyrimidine is optionally substituted with one or more substituentsindependently selected from the group consisting of alkyl andhydroxyalkyl.
 21. The compound according to claim 20, wherein thecompound has the structure of Formula (IV):

wherein: R¹ is methyl, bromo or chloro; R⁴ is —H, chloro or methyl; R⁵⁰is —H or methyl; and R⁵¹ is —H, methyl or hydroxy.
 22. The compoundaccording to claim 21, selected from the group consisting of:4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((2,4-difluorobenzyl)oxy)-2″-(2-hydroxypropan-2-yl)-5′,6-dimethyl-2H-[1,4′:2′,4″-terpyridin]-2-one;and2″-(tert-butyl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′:2′,4″-terpyridin]-2-one.23. The compound according to claim 21, selected from the groupconsisting of:3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((2,4-difluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((2,4-difluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((2,4-difluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;4-((2,4-difluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;and4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one.24. The compound according to claim 1, wherein X is N and Y is CH. 25.The compound according to claim 24, wherein: R¹ is selected from thegroup consisting of C₁-C₃-alkyl, bromo, chloro and fluoro; R² is alkoxyoptionally substituted with one or more substituents selected from thegroup consisting of cycloalkyl and aryl; wherein the cycloalkyl or arylis optionally substituted with one or more substituents independentlyselected from the group consisting of C₁-C₃-alkyl and halo; R³ and R⁴are independently C₁-C₃-alkyl and —H; and R⁵ is heterocyclyl optionallysubstituted with one or more substituents independently selected fromthe group consisting of alkyl, hydroxyalkyl and aminoalkyl.
 26. Thecompound according to claim 25, wherein: R¹ is methyl or chloro; R² isalkoxy optionally substituted with phenyl optionally substituted withone or more halo substituents; R³ is methyl; R⁴ is —H or methyl; and R⁵is five- or six-membered heteroaryl optionally substituted with one ormore substituents independently selected from the group consisting ofalkyl and hydroxyalkyl.
 27. The compound according to claim 26, wherein:R² is alkoxy substituted with phenyl optionally substituted with one ormore substituents independently selected from the group consisting ofchloro and fluoro; and R⁵ is pyridine or pyrimidine, wherein thepyridine or pyrimidine is optionally substituted with one or moresubstituents independently selected from the group consisting of alkyland hydroxyalkyl.
 28. The compound according to claim 27, wherein thecompound has the structure of Formula (V):

wherein: Z is selected from the group consisting of CH and N; R¹ ismethyl or chloro; R⁴ is —H or methyl; and R⁵¹ is methyl or hydroxy. 29.The compound according to claim 28, selected from the group consistingof:4-((2,4-difluorobenzyl)oxy)-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-2H-[1,3′-bipyridin]-2-one;4-((2,4-difluorobenzyl)oxy)-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,3,6-trimethyl-2H-[1,3′-bipyridin]-2-one;3-chloro-4-((2,4-difluorobenzyl)oxy)-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,3′-bipyridin]-2-one;3-chloro-4-((2,4-difluorobenzyl)oxy)-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,6-dimethyl-2H-[1,3′-bipyridin]-2-one;5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,3′-bipyridin]-2-one;5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-2′,6-dimethyl-2H-[1,3′-bipyridin]-2-one;3-chloro-4-((2,4-difluorobenzyl)oxy)-2″-(2-hydroxypropan-2-yl)-6-methyl-2H-[1,3′:5′,4″-terpyridin]-2-one;3-chloro-4-((2,4-difluorobenzyl)oxy)-2″-(2-hydroxypropan-2-yl)-2′,6-dimethyl-2H-[1,3′:5′,4″-terpyridin]-2-one;2″-(tert-butyl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-6-methyl-2H-[1,3′:5′,4″-terpyridin]-2-one;and2″-(tert-butyl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-2′,6-dimethyl-2H-[1,3′:5′,4″-terpyridin]-2-one.30. The compound according to claim 1, wherein: X and Y areindependently selected from the group consisting of CH and N, with theproviso that when X is CH, Y is N, and when X is N, Y is CH; R¹ isselected from the group consisting of C₁-C₃-alkyl, bromo, chloro andfluoro; R² is alkoxy, optionally substituted with one or moresubstituents selected from the group consisting of cycloalkyl and aryl;wherein the cycloalkyl or aryl is optionally substituted with one ormore substituents independently selected from the group consisting ofC₁-C₃-alkyl and halo; R³ and R⁴ are independently C₁-C₃-alkyl, halo and—H; and R⁵ is heterocyclyl optionally substituted with one or moresubstituents independently selected from the group consisting of alkyl,hydroxyalkyl and aminoalkyl.
 31. The compound according to claim 30,wherein: R¹ is methyl, bromo or chloro; R² is alkoxy optionallysubstituted with phenyl optionally substituted with one or more halosubstituents; R³ is methyl; R⁴ is —H, chloro or methyl; and R⁵ is five-or six-membered heteroaryl optionally substituted with one or moresubstituents independently selected from the group consisting of alkyland hydroxyalkyl.
 32. The compound according to claim 31, wherein: R² isalkoxy substituted with phenyl optionally substituted with one or moresubstituents independently selected from the group consisting of chloroand fluoro; and R⁵ is pyridine or pyrimidine, wherein the pyridine orpyrimidine is optionally substituted with one or more substituentsindependently selected from the group consisting of alkyl andhydroxyalkyl.
 33. The compound according to claim 32, wherein thecompound has the structure of Formula (VI):

wherein: X and Y are independently selected from the group consisting ofCH and N, with the proviso that when X is CH, Y is N, and when X is N, Yis CH; R¹ is methyl, bromo or chloro; R⁴ is —H, chloro or methyl; R⁵⁰ is—H or methyl; and R⁵¹ is —H, methyl or hydroxy.
 34. The compoundaccording to claim 33, selected from the group consisting of:3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((4-fluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((4-fluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((4-fluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((4-fluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((4-fluorobenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((4-fluorobenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;4-((4-fluorobenzyl)oxy)-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;4-((4-fluorobenzyl)oxy)-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-2H-[1,4′-bipyridin]-2-one;and4-((4-fluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one.35. A compound according to claim 1, wherein: X and Y are independentlyselected from the group consisting of CH and N, with the proviso thatwhen X is CH, Y is N, and when X is N, Y is CH; R¹ is selected from thegroup consisting of C₁-C₃-alkyl, bromo, chloro and fluoro; R² is alkoxy,optionally substituted with one or more substituents selected from thegroup consisting of cycloalkyl and aryl; wherein the cycloalkyl or arylis optionally substituted with one or more substituents independentlyselected from the group consisting of C₁-C₃-alkyl and C₁-C₃-alkoxy; R³and R⁴ are independently C₁-C₃-alkyl, halo and —H; and R⁵ isheterocyclyl optionally substituted with one or more substituentsindependently selected from the group consisting of alkyl, hydroxyalkyland aminoalkyl.
 36. The compound according to claim 35, wherein: R¹ ismethyl, bromo or chloro; R² is alkoxy optionally substituted with phenyloptionally substituted with one or more substituents independentlyselected from the group consisting of C₁-C₃-alkyl and C₁-C₃-alkoxy; R³is methyl; R⁴ is —H, chloro or methyl; and R⁵ is five- or six-memberedheteroaryl optionally substituted with one or more substituentsindependently selected from the group consisting of alkyl andhydroxyalkyl.
 37. A compound according to claim 36, wherein: R² isalkoxy substituted with phenyl optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁-C₃-alkyl and C₁-C₃-alkoxy; and R⁵ is pyridine or pyrimidine, whereinthe pyridine or pyrimidine is optionally substituted with one or moresubstituents independently selected from the group consisting of alkyland hydroxyalkyl.
 38. The compound according to claim 37, wherein thecompound has the structure of Formula (VII):

wherein: X and Y are independently selected from the group consisting ofCH and N, with the proviso that when X is CH, Y is N, and when X is N, Yis CH; R¹ is methyl, bromo or chloro; R⁴ is —H, chloro or methyl; R²¹ ismethyl or methoxy; R⁵⁰ is —H or methyl; and R⁵¹ is —H, methyl orhydroxy.
 39. The compound according to claim 38, selected from the groupconsisting of:3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one;and2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((3-methylbenzyl)oxy)-2H-[1,4′-bipyridin]-2-one.40. The compound according to claim 38, selected from the groupconsisting of:3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;and2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((3-methoxybenzyl)oxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one.41. The compound according to claim 1, wherein: X and Y areindependently selected from the group consisting of CH and N, with theproviso that when X is CH, Y is N, and when X is N, Y is CH; R¹ isselected from the group consisting of C₁-C₃-alkyl, bromo, chloro andfluoro; R² is alkoxy, optionally substituted with one or moreheterocyclyl substituents optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁-C₃-alkyl, C₁-C₃-alkoxy and cyano; R³ is C₁-C₃-alkyl; R⁴ is selectedfrom the group consisting of —H, C₁-C₃-alkyl, bromo, chloro and fluoro;and R⁵ is heterocyclyl optionally substituted with one or moresubstituents independently selected from the group consisting of alkyl,hydroxyalkyl and aminoalkyl.
 42. The compound according to claim 41,wherein: R¹ is methyl, bromo or chloro; R² is alkoxy optionallysubstituted with five- or six-membered heteroaryl optionally substitutedwith one or more substituents independently selected from the groupconsisting of C₁-C₃-alkyl and C₁-C₃-alkoxy; R³ is methyl; R⁴ is —H,methyl or chloro; and R⁵ is five- or six-membered heteroaryl optionallysubstituted with one or more substituents independently selected fromthe group consisting of alkyl and hydroxyalkyl.
 43. The compoundaccording to claim 42, wherein: R² is alkoxy substituted withsix-membered heteroaryl optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁-C₃-alkyl and C₁-C₃-alkoxy; and R⁵ is pyridine or pyrimidine, whereinthe pyridine or pyrimidine is optionally substituted with one or moresubstituents independently selected from the group consisting of alkyland hydroxyalkyl.
 44. The compound according to claim 43, wherein thecompound has the structure of Formula (VIII):

wherein: X and Y are independently selected from the group consisting ofCH and N, with the proviso that when X is CH, Y is N, and when X is N, Yis CH; R¹ is methyl, bromo or chloro; R⁴ is —H, methyl or chloro; R²¹ ismethyl or methoxy; R⁵⁰ is —H or methyl; and R⁵¹ is —H, methyl orhydroxy.
 45. The compound according to claim 44, selected from the groupconsisting of:3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;and2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one.46. The compound according to claim 44, selected from the groupconsisting of:3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-isopropyl-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one;2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,5′,6-trimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one;3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-6-methyl-2H-[1,4′-bipyridin]-2-one;and2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-4-((6-methoxypyridin-2-yl)methoxy)-3,6-dimethyl-2H-[1,4′-bipyridin]-2-one.47. A compound of3-chloro-4-((2,4-difluorobenzyl)oxy)-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one,or a pharmaceutically acceptable salt thereof.
 48. A compound of2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-4-((2,4-difluorobenzyl)oxy)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one,or a pharmaceutically acceptable salt thereof.
 49. A pharmaceuticalcomposition comprising a therapeutically effective amount of a compoundof claim 1 or a pharmaceutically acceptable salt thereof, and apharmaceutically acceptable carrier.
 50. The pharmaceutical compositionof claim 49, further comprising a therapeutically effective amount of anactive pharmaceutical ingredient selected from the group consisting ofanti-inflammatory drugs, anti-atherosclerotic drugs, immunosuppressivedrugs, immunomodulatory drugs, cytostatic drugs, angiogenesisinhibitors, kinase inhibitors, cytokine blockers and inhibitors of celladhesion molecules.
 51. A method for treating a condition comprisingadministering to a subject in need thereof a therapeutically effectiveamount of a compound of claim 1 or pharmaceutically acceptable saltthereof, wherein the condition is selected from the group consisting ofautoimmune disorders, chronic inflammatory disorders, acute inflammatorydisorders, auto-inflammatory disorders, atherosclerosis, diabetes,fibrotic diseases, metabolic disorders, cancer, neoplasia, leukemia andlymphoma.
 52. The method of claim 51, wherein the subject is a mammalselected from a canine and a humane.
 53. The method of claim 52, whereinthe condition is lymphoma.